LDLR

Summary

LDLR (low density lipoprotein receptor, HGNC:6547) is a protein-coding gene on chromosome 19p13.2, encoding Low-density lipoprotein receptor (P01130). Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. It is a selective cancer dependency (DepMap: 10.8% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

The low density lipoprotein receptor (LDLR) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. The encoded protein is normally bound at the cell membrane, where it binds low density lipoprotein/cholesterol and is taken into the cell. Lysosomes release the cholesterol, which is made available for repression of microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting step in cholesterol synthesis. At the same time, a reciprocal stimulation of cholesterol ester synthesis takes place. Mutations in this gene cause the autosomal dominant disorder, familial hypercholesterolemia. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 3949 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypercholesterolemia, familial, 1 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 194 (top 1% of genes corpus-wide)
• Clinical variants (ClinVar): 4,904 total — 1236 pathogenic, 641 likely-pathogenic (top 1% of genes corpus-wide)
• GTEx eGene: eQTL in 13 tissues, sQTL in 13 (q < 0.05)
• Phenotypes (HPO): 37
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 10.8% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.09 (unconstrained)
• MANE Select transcript: NM_000527
• Interaction hub: 3,275 STRING partners (top 2% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6547
Approved symbol	LDLR
Name	low density lipoprotein receptor
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	LDLCQ2
Ensembl gene	ENSG00000130164
Ensembl biotype	protein_coding
OMIM	606945
Entrez	3949

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 27 protein_coding, 7 nonsense_mediated_decay, 4 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000558518

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 2: 6, TSL 3: 3, TSL 5: 2

ENST00000558518, ENST00000252444, ENST00000455727, ENST00000535915, ENST00000545707, ENST00000557933, ENST00000557958, ENST00000558013, ENST00000558528, ENST00000559340, ENST00000560173, ENST00000560467, ENST00000560502, ENST00000560628, ENST00000713991, ENST00000856645, ENST00000856646, ENST00000856647, ENST00000856648, ENST00000913405, ENST00000913406, ENST00000913407, ENST00000913408, ENST00000913409, ENST00000913410, ENST00000913411, ENST00000913412, ENST00000942040, ENST00001047212, ENST00001047213, ENST00001064478, ENST00001064479, ENST00001064480, ENST00001109383, ENST00001109384, ENST00001113025, ENST00001113026, ENST00001128405, ENST00001142759

RefSeq mRNA: 5 — MANE Select: NM_000527 NM_000527, NM_001195798, NM_001195799, NM_001195800, NM_001195803

CCDS: CCDS12254, CCDS56083, CCDS56084, CCDS56085, CCDS58651

Canonical transcript exons

ENST00000558518 — 18 exons

Exon	Start	End
ENSE00002553919	11131281	11133820
ENSE00002568469	11113278	11113449
ENSE00003463530	11120370	11120522
ENSE00003464579	11120092	11120233
ENSE00003482036	11116859	11116998
ENSE00003501255	11123174	11123344
ENSE00003509370	11113535	11113762
ENSE00003604878	11116094	11116212
ENSE00003629410	11128008	11128085
ENSE00003652085	11089463	11089615
ENSE00003680438	11129513	11129670
ENSE00004011958	11110652	11110771
ENSE00004011963	11100223	11100345
ENSE00004011965	11105220	11105600
ENSE00004011966	11102664	11102786
ENSE00004011967	11107392	11107514
ENSE00004011968	11111514	11111639
ENSE00004011970	11106565	11106687

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 99.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.1962 / max 582.4371, expressed in 1807 samples.

Highest expression (Bgee): adrenal tissue, lower lobe of lung, adrenal gland, adrenal gland cortex, endometrium epithelium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LDLR is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 13 tissues and its splicing (sQTL) in 13 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 26 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells EBV-transformed lymphocytes	sqtl	3.2e-07	+0.56	19:11118542:A:G
Esophagus Mucosa	sqtl	2.5e-06	+0.27	19:11116650:C:G
Adipose Visceral Omentum	sqtl	4.2e-06	+0.29	19:11116650:C:G
Lung	sqtl	1.1e-05	+0.26	19:11116926:C:T
Brain Cerebellum	sqtl	6.7e-05	+0.56	19:11116650:C:G
Skin Sun Exposed Lower leg	sqtl	8.1e-05	+0.27	19:11125504:C:A
Nerve Tibial	eqtl	2.9e-04	+0.69	19:11120527:G:A
Cells Cultured fibroblasts	eqtl	4.6e-04	+0.44	19:11120527:G:A
Cells EBV-transformed lymphocytes	eqtl	4.8e-04	+0.95	19:11120527:G:A
Whole Blood	eqtl	6.7e-04	+0.64	19:11120527:G:A
Brain Cerebellar Hemisphere	sqtl	1.2e-03	+0.40	19:11116804:A:C
Artery Tibial	eqtl	2.1e-03	+0.15	19:10950639:G:A
Skin Not Sun Exposed Suprapubic	eqtl	3.1e-03	+0.60	19:11120527:G:A
Stomach	eqtl	4.1e-03	-0.16	19:11122919:TC:T
Esophagus Mucosa	eqtl	5.1e-03	+0.50	19:11120527:G:A
Brain Spinal cord cervical c-1	eqtl	6.4e-03	-0.31	19:10228088:A:G
Brain Hippocampus	eqtl	6.6e-03	+0.96	19:11120527:G:A
Nerve Tibial	sqtl	8.8e-03	+0.22	19:11116394:C:T
Pancreas	eqtl	9.3e-03	+0.25	19:11077477:A:C
Spleen	eqtl	1.0e-02	+1.16	19:11120527:G:A

FANTOM5 promoters

showing 10 of 12 alternative TSS:

Promoter ID	TPM avg	Samples expressed
173893	33.3337	1761
173894	7.9618	1657
173897	2.0449	776
173895	1.6665	964
173896	1.3827	805
173901	1.2044	418
173902	1.1728	531
173891	0.8366	537
173892	0.6454	377
208690	0.4955	262

Top tissues by expression

showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	99.53	gold quality
lower lobe of lung	UBERON:0008949	97.66	gold quality
right adrenal gland	UBERON:0001233	96.45	gold quality
adrenal gland	UBERON:0002369	96.21	gold quality
right adrenal gland cortex	UBERON:0035827	96.05	gold quality
left adrenal gland	UBERON:0001234	95.85	gold quality
endometrium epithelium	UBERON:0004811	95.75	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.66	gold quality
adrenal cortex	UBERON:0001235	95.48	gold quality
left adrenal gland cortex	UBERON:0035825	95.31	gold quality
stromal cell of endometrium	CL:0002255	95.30	gold quality
upper lobe of lung	UBERON:0008948	95.17	gold quality
upper lobe of left lung	UBERON:0008952	95.09	gold quality
lung	UBERON:0002048	94.52	gold quality
mucosa of urinary bladder	UBERON:0001259	94.34	gold quality
right lung	UBERON:0002167	93.94	gold quality
esophagus mucosa	UBERON:0002469	93.66	gold quality
lower esophagus mucosa	UBERON:0035834	93.61	gold quality
islet of Langerhans	UBERON:0000006	93.28	gold quality
left uterine tube	UBERON:0001303	93.21	gold quality
pharyngeal mucosa	UBERON:0000355	92.79	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.79	gold quality
ventricular zone	UBERON:0003053	92.77	gold quality
cartilage tissue	UBERON:0002418	92.67	gold quality
cervix epithelium	UBERON:0004801	92.43	gold quality
liver	UBERON:0002107	92.39	gold quality
decidua	UBERON:0002450	92.36	gold quality
oral cavity	UBERON:0000167	92.09	gold quality
gingival epithelium	UBERON:0001949	91.83	gold quality
amniotic fluid	UBERON:0000173	91.73	gold quality
right ovary	UBERON:0002118	91.73	gold quality
gingiva	UBERON:0001828	91.65	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.49	gold quality
embryo	UBERON:0000922	91.40	gold quality
right lobe of liver	UBERON:0001114	91.31	gold quality
left ovary	UBERON:0002119	91.16	gold quality
bronchial epithelial cell	CL:0002328	91.12	gold quality
epithelium of bronchus	UBERON:0002031	90.81	gold quality
bronchus	UBERON:0002185	90.78	gold quality
colonic epithelium	UBERON:0000397	90.74	gold quality
trachea	UBERON:0003126	90.67	gold quality
esophagus	UBERON:0001043	90.44	gold quality
ganglionic eminence	UBERON:0004023	90.43	gold quality
pericardium	UBERON:0002407	90.38	gold quality
uterine cervix	UBERON:0000002	90.30	gold quality
gall bladder	UBERON:0002110	90.30	gold quality
mammalian vulva	UBERON:0000997	90.07	gold quality
placenta	UBERON:0001987	89.83	gold quality
colonic mucosa	UBERON:0000317	89.77	gold quality
ectocervix	UBERON:0012249	89.77	gold quality
mucosa of transverse colon	UBERON:0004991	89.75	gold quality
squamous epithelium	UBERON:0006914	89.60	gold quality
epithelium of esophagus	UBERON:0001976	89.47	gold quality
omental fat pad	UBERON:0010414	89.46	gold quality
skin of abdomen	UBERON:0001416	89.45	gold quality
peritoneum	UBERON:0002358	89.44	gold quality
sural nerve	UBERON:0015488	89.31	gold quality
body of stomach	UBERON:0001161	89.20	gold quality
smooth muscle tissue	UBERON:0001135	89.18	gold quality
duodenum	UBERON:0002114	88.96	gold quality
esophagus squamous epithelium	UBERON:0006920	88.70	gold quality
upper leg skin	UBERON:0004262	88.67	gold quality
stomach	UBERON:0000945	88.65	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.61	gold quality
pigmented layer of retina	UBERON:0001782	88.45	gold quality
jejunal mucosa	UBERON:0000399	88.42	gold quality
saphenous vein	UBERON:0007318	88.27	gold quality
visceral pleura	UBERON:0002401	88.06	gold quality
vena cava	UBERON:0004087	87.95	gold quality
pancreas	UBERON:0001264	87.82	gold quality
skin of leg	UBERON:0001511	87.76	gold quality
zone of skin	UBERON:0000014	87.72	gold quality
ovary	UBERON:0000992	87.67	gold quality
vermiform appendix	UBERON:0001154	87.56	gold quality
dorsal root ganglion	UBERON:0000044	87.40	gold quality
mouth mucosa	UBERON:0003729	87.17	gold quality
vagina	UBERON:0000996	87.06	gold quality
transverse colon	UBERON:0001157	87.01	gold quality
epithelial cell of pancreas	CL:0000083	86.81	gold quality
endocervix	UBERON:0000458	86.80	gold quality
lower esophagus	UBERON:0013473	86.78	gold quality
body of uterus	UBERON:0009853	86.77	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.73	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.71	gold quality
small intestine	UBERON:0002108	86.52	gold quality
minor salivary gland	UBERON:0001830	86.46	gold quality
cervix squamous epithelium	UBERON:0006922	86.38	silver quality
urinary bladder	UBERON:0001255	86.33	gold quality
large intestine	UBERON:0000059	86.21	gold quality
intestine	UBERON:0000160	86.20	gold quality
colon	UBERON:0001155	86.15	gold quality
heart right ventricle	UBERON:0002080	85.99	gold quality
sigmoid colon	UBERON:0001159	85.58	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.54	gold quality
female reproductive system	UBERON:0000474	85.44	gold quality
trigeminal ganglion	UBERON:0001675	85.37	gold quality
saliva-secreting gland	UBERON:0001044	85.31	gold quality
right atrium auricular region	UBERON:0006631	85.26	gold quality
cauda epididymis	UBERON:0004360	85.16	gold quality
prostate gland	UBERON:0002367	85.04	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	946.56
E-GEOD-130148	yes	10.99
E-MTAB-7316	no	483.72
E-GEOD-124858	no	69.90
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	56.4	medium
Choroid plexus	tissue	54.1
Lung	tissue	51.7	medium
Adrenal gland	tissue	51.5	medium
Spinal cord	tissue	50.4
Pancreas	tissue	47.9	not detected
Locus coeruleus	tissue	43.2
Adipose tissue	tissue	40.8	not detected
Corpus callosum	tissue	38.2
Medulla oblongata	tissue	35.7
Gallbladder	tissue	34.6	low
Stomach 1	tissue	34.5	medium
Esophagus	tissue	33.4	not detected
Substantia nigra	tissue	29.5
Pons	tissue	28.7
Smooth muscle	tissue	26.7	not detected
Midbrain	tissue	26.4
Periaqueductal gray	tissue	26.2
Bone marrow	tissue	25.8	not detected
Appendix	tissue	25.7	not detected
Superior colliculi	tissue	24.6
Vagina	tissue	24.4	not detected
Thalamus	tissue	23.6
Hypothalamus	tissue	22.9
Duodenum	tissue	22.2	medium
Postcentral gyrus	tissue	21.1
Urinary bladder	tissue	21.0	medium
Hippocampus	tissue	20.5	not detected
Prostate	tissue	19.0	not detected
Hippocampal formation	tissue	18.8
Colon	tissue	18.1	medium
Cerebral cortex	tissue	18.0	low
Insular cortex	tissue	18.0
Cervix	tissue	17.2	not detected
Amygdala	tissue	17.2
Small intestine	tissue	17.2	low
Retrosplenial cortex	tissue	17.1
Prefrontal cortex	tissue	16.9
Motor cortex	tissue	16.5
Retrosplenial and cingulate cortex	tissue	16.2
Placenta	tissue	15.6	not detected
Entorhinal cortex	tissue	15.2
Occipital cortex	tissue	15.0
Septum	tissue	14.9
Temporal cortex	tissue	14.7
Ventral forebrain	tissue	14.6
Somatosensory cortex	tissue	14.5
Endometrium 1	tissue	14.2	not detected
Olfactory bulb	tissue	13.1
Ovary	tissue	12.2	not detected
Breast	tissue	12.0	low
Rectum	tissue	11.5	not detected
Salivary gland	tissue	10.8	not detected
Putamen	tissue	10.6
Frontal cortex	tissue	10.4
Spleen	tissue	9.9	not detected
Caudate putamen	tissue	9.8
Basal ganglia	tissue	9.7	low
Parathyroid gland	tissue	9.5	low
Cerebellum	tissue	9.0	low

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Nucleus gracilis (59.4), Motor hypoglossal nucleus (51.3), Ventral spinal cord (50.4), Reticular pontine nucleus, caudal (49.0), Nucleus raphe magnus (47.7).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets:

Target	Regulation
ICAM1	Activation
SOCS5	Activation

Upstream regulators (CollecTRI, top): ATF3, BMAL1, CEBPA, CEBPB, CEBPG, CNBP, CREB1, CREBBP, DGKQ, DNMT1, EGR1, ESR1, ESR2, FOS, HES1, HES6, HNF4A, HNRNPK, IKZF1, KLF13, KLF4, KLF9, NFYA, NR1H3, PPARA, PPARG, PPARGC1A, RXRA, SP1, SP3, SREBF1, SREBF2, THRB, TXK, YY1, ZBTB17

miRNA regulators (miRDB)

Targeting LDLR by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 96 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-128-3P	99.95	71.17	2484
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-6783-3P	99.89	67.92	2059

Functional genomics

gnomAD constraint: pLI 1.25e-30, LOEUF 1.09, missense Z 0.605 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000558518 — one region, missense o/e 1.00. ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 10.8% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): U-937 (-1.915), KMS-20 (-1.298), Mero-83 (-1.156), BC-2 (-1.127), P30/OHK (-1.072), SNU-719 (-1.056), Evsa-T (-1.049), HT (-1.01), TE-4 (-1.001), EJM (-0.946), MOR/CPR (-0.936), HEL 92.1.7 (-0.929), C75 (-0.916), G-401 (-0.901), HCC515 (-0.883).

Literature-anchored findings (GeneRIF, showing 40)

• mutations in German patients with familial hypercholesterolemia (PMID:11462246)
• Nineteen mutations were novel: two nonsense, five missense, six nucleotide(s) insertions and six nucleotide(s) deletions. (PMID:11524740)
• mutations in Canadian subjects with familial hypercholesterolemia, but not of French descent (PMID:11668627)
• novel mutations in patients with familial hypercholesterolemia in Spain (PMID:11668640)
• HDL cholesterol levels in patients with molecularly defined familial hypercholesterolemia. LDL receptor gene mutation (81T>G, 858C>A, 1285G>A, 1646G>A, and 1775G>A,) did not significantly influence HDL cholesterol levels. (PMID:11848618)
• These results suggested that polymorphisms of LDL-Rgene might play an independent role of risk factor for hyperlipidemia. (PMID:11860839)
• Eight novel mutations and functional impairments are identified in familial hypercholesterolemia in the north of Japan. (PMID:11916007)
• Review. The proposed association between apoB secretion and FH may, however, be a function of the class of LDL receptor defect. (PMID:11923121)
• LDLR mutations in 350 cases of FH revealed 34 missense, 10 nonsense, 18 frameshift, 2 inframe, 10 splice, and 2 promoter mutations and 10 rearrangements. (PMID:11923123)
• Molecular basis of familial hypercholesterolemia in Brazil: Identification of seven novel LDLR gene mutations (PMID:11933210)
• Defective LDL receptors give rise to a phenotype of elevated LDL cholesterol. Disturbances in IDL metabolism provide the basis for understanding why FDB is less severe than FH. An apoB-LDL receptor interaction is important in the IDL to LDL conversion. (PMID:11947895)
• Critical role of diacylglycerol- and phospholipid-regulated protein kinase C epsilon in induction of low-density lipoprotein receptor transcription in response to depletion of cholesterol. (PMID:11997513)
• Influence of an asparagine to lysine mutation at amino acid 3516 of apolipoprotein B on low-density lipoprotein receptor binding. (PMID:12031600)
• apoE binds to the LDL receptor by interacting with more than one of the receptor ligand-binding repeats. (PMID:12036962)
• human rhinovirus serotype 1A (HRV1A)does not bind to the LDL receptor (PMID:12072496)
• bile acids affect gene expression via a MAPK cascade-mediated stabilization of mRNA (PMID:12149270)
• ARH functions as an adaptor protein that couples LDLR to the endocytic machinery (PMID:12221107)
• Egr1 is the oncostatin M-induced transcription factor that binds to the SIRE sequence of the LDLR promoter (PMID:12235180)
• Two novel missense mutations in the LDL-R gene causing FH were found in two unrelated families from central and southern Tunisia. (PMID:12414836)
• Double mutant allele was founded in 10 out of 458 unrelated patients and not all carriers of the double mutant allele develop hypercholesterolemia. (PMID:12442279)
• crystal structure of the extracellular portion of LDL-R at pH = 5.3 and at 3.7 A resolution; this structure should represent the conformation of LDL-R adopted in endosomes (PMID:12459547)
• restoration of function in cells from patients with autosomal recessive hypercholesterolemia by retroviral expression of ARH1 (PMID:12464675)
• A novel mutation of LDLR gene was reported. This mutation may severely affect the function of LDLR. (PMID:12485531)
• productive LDL-R folding in a cell is not vectorial but is mostly posttranslational, and involves transient long-range non-native disulfide bonds that are isomerized into native short-range cysteine pairs (PMID:12493918)
• fatty acids and rosiglitazone directly stimulate transcription of the LRP gene through activation of PPARgamma and increase functional LRP expression. (PMID:12551936)
• pp90RSK- and protein kinase C-dependent pathway regulates p42/44MAPK-induced LDL receptor transcription in HepG2 cells. (PMID:12562867)
• Deletion in low-density lipoprotein receptor gene is associated with severe familial hypercholesterolemia (PMID:12705331)
• Insulin plays an important role in the in vivo expression of LDL receptors on monocyte cell surface. (PMID:12716819)
• mutation spectrum of the LDLR gene among patients with familial hypercholesterolemia in Morocco (PMID:12730724)
• a new mutation is found, in which a serine residue was replaced by a cysteine at amino acid position 305 (S305C) (PMID:12820708)
• The allelic distribution of the (TA)n polymorphism was significantly different between migraine without aura (MO) and both controls and migraine with aura (MA). (PMID:12873747)
• data presented raise the possibility that the -175g–>t polymorphism in the promoter region of the LDLR gene may have subtle effects that become clinically important within certain genetic and/or environmental contexts (PMID:12944120)
• study provides strong evidence that early growth response 1 regulates low density lipoprotein receptor transcription via a novel mechanism of protein-protein interaction with CCAAT enhancer-binding protein beta (PMID:12947119)
• Doubling transfected human Ldlr expression caused severe atherosclerosis with marked accumulation of cholesterol-rich, apoE-poor remnants in mice with human apoE4, but not apoE3, suggesting that the receptor can trap apoE4. (PMID:12969990)
• data provide an alternative mechanism of LDL receptor gene expression by non-classical estradiol- and tamoxifen-stimulated induction through an ER-alpha/Sp1 complex (PMID:14568562)
• The mean of carotid artery intima-media maximum thicknesses was significantly higher in the 2312-3 C–>A group than in patients with other LDLr mutations (PMID:14624402)
• patients with familial hypercholesterolemia carrying the null LDL receptor have elevation of plasma LDL-cholesterol attributable to both decreased clearance of LDL and increased hepatic production of apoB-100-containing lipoproteins (PMID:14967814)
• cell surface levels of the LDLR mutants were significantly increased upon inhibition of the proteasome degradation pathway (PMID:14993243)
• Point mutations in low density lipoprotein receptor is associated with severe hypercholesterolemia (PMID:15015036)
• a rapid diagnostic assay capable of simultaneously analyzing seven point mutations in the low-density lipoprotein receptor (LDLR) gene, which occur at high frequency in South African familial hypercholesterolemia patients. (PMID:15068387)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-258f14.3	ENSDARG00000075974
danio_rerio	si:dkey-258f14.7	ENSDARG00000095925
mus_musculus	Ldlr	ENSMUSG00000032193
rattus_norvegicus	Ldlr	ENSRNOG00000009946
drosophila_melanogaster	arr	FBGN0000119
drosophila_melanogaster	Ndg	FBGN0026403

Paralogs (14): LRP6 (ENSG00000070018), LRP2 (ENSG00000081479), NID2 (ENSG00000087303), NID1 (ENSG00000116962), LRP1 (ENSG00000123384), LRP3 (ENSG00000130881), LRP4 (ENSG00000134569), EGF (ENSG00000138798), LRP12 (ENSG00000147650), VLDLR (ENSG00000147852), LRP8 (ENSG00000157193), LRP5 (ENSG00000162337), LRP1B (ENSG00000168702), LRP10 (ENSG00000197324)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:96765) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 77 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased circulating cholesterol level	16
increased circulating LDL cholesterol level	9
increased susceptibility to atherosclerosis	7
increased circulating triglyceride level	6
atherosclerotic lesions	6
increased circulating HDL cholesterol level	4
increased circulating VLDL cholesterol level	4
abnormal circulating cholesterol level	3
abnormal spatial learning	3
increased liver cholesterol level	3
abnormal microglial cell morphology	2
hyperglycemia	2
increased circulating insulin level	2
hepatic steatosis	2
abnormal cholesterol homeostasis	2
impaired glucose tolerance	2
abnormal short-term spatial reference memory	2
abnormal synaptic bouton morphology	2
increased liver triglyceride level	2
increased grip strength	2
abnormal circulating LDL cholesterol level	1
decreased circulating HDL cholesterol level	1
abnormal triglyceride level	1
alopecia	1
abnormal liver physiology	1

+52 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Oryctolagus cuniculus	P35953	95.3%	Diamond
Bos taurus	P01131	92.6%	Diamond
Sus scrofa	Q28832	92.6%	Diamond
Camponotus floridanus	E2AX35	88.6%	Diamond
Xenopus laevis	Q99087	87.6%	Diamond
Cricetulus griseus	P35950	87.0%	Diamond
Gallus gallus	P98165	82.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LDLR-AS1	ncRNA	115271120
SPC24	protein-coding	147841
KANK2	protein-coding	25959
SMARCA4	protein-coding	6597
MIR6886	ncRNA	102465534
CARM1	protein-coding	10498
YIPF2	protein-coding	78992
TIMM29	protein-coding	90580
DOCK6-AS1	ncRNA	105372273
ANGPTL8	protein-coding	55908
DOCK6	protein-coding	57572
C19orf38	protein-coding	255809

Protein

Protein identifiers

Low-density lipoprotein receptor — P01130 (reviewed: P01130)

All UniProt accessions (6): P01130, A0AAQ5BHB8, H0YM92, H0YMD1, H0YMQ3, J3KMZ9

UniProt curated annotations — full annotation on UniProt →

Function. Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. Forms a ternary complex with PGRMC1 and TMEM97 receptors which increases LDLR-mediated LDL internalization. (Microbial infection) Acts as a receptor for hepatitis C virus in hepatocytes, but not through a direct interaction with viral proteins. (Microbial infection) Acts as a receptor for Vesicular stomatitis virus. (Microbial infection) In case of HIV-1 infection, may function as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells. (Microbial infection) Acts as a receptor for Crimean-Congo hemorrhagic fever virus (CCHFV). (Microbial infection) Acts as a receptor for many Alphavirus, including Getah virus (GETV), Ross river virus (RRV) and Semliki Forest virus.

Subunit / interactions. Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. Interacts (via NPXY motif) with LDLRAP1 (via PID domain). Interacts with ARRB1. Interacts with SNX17. Interacts with the full-length immature form of PCSK9 (via C-terminus). Interacts with PGRMC1 and TMEM97; the interaction increases LDL internalization. (Microbial infection) Interacts with C.difficile toxin TcdA, suggesting that it may contribute to TcdA toxin entry into cells. (Microbial infection) Interacts with vesicular stomatitis virus glycoprotein. (Microbial infection) Interacts with Crimean-Congo hemorrhagic fever virus (CCHFV) glycoprotein C. (Microbial infection) Interacts with Getah virus (GETV) E2-E1 spike protein complex. (Microbial infection) May interact with HIV-1 Tat.

Subcellular location. Cell membrane. Membrane. Clathrin-coated pit. Golgi apparatus. Early endosome. Late endosome. Lysosome.

Post-translational modifications. N- and O-glycosylated. Ubiquitinated by MYLIP leading to degradation.

Disease relevance. Hypercholesterolemia, familial, 1 (FHCL1) [MIM:143890] A form of hypercholesterolemia, a disorder of lipoprotein metabolism characterized by elevated serum low-density lipoprotein (LDL) cholesterol levels, which result in excess deposition of cholesterol in tissues and leads to xanthelasma, xanthomas, accelerated atherosclerosis and increased risk of premature coronary heart disease. FHCL1 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The NPXY motif mediates the interaction with the clathrin adapter DAB2 and with LDLRAP1 which are involved in receptor internalization. A few residues outside the motif also play a role in the interaction.

Similarity. Belongs to the LDLR family.

Isoforms (6)

UniProt ID	Names	Canonical?
P01130-1	1	yes
P01130-2	2
P01130-3	3
P01130-4	4
P01130-5	5
P01130-6	6

RefSeq proteins (5): NP_000518, NP_001182727, NP_001182728, NP_001182729, NP_001182732 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000033	LDLR_classB_rpt	Repeat
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR002172	LDrepeatLR_classA_rpt	Repeat
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR011042	6-blade_b-propeller_TolB-like	Homologous_superfamily
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR023415	LDLR_class-A_CS	Conserved_site
IPR036055	LDL_receptor-like_sf	Homologous_superfamily
IPR049883	NOTCH1_EGF-like	Domain
IPR051221	LDLR-related	Family

Pfam: PF00057, PF00058, PF07645, PF14670

UniProt features (395 total): sequence variant 195, strand 71, disulfide bond 30, turn 22, helix 19, mutagenesis site 17, domain 10, splice variant 7, repeat 6, glycosylation site 5, region of interest 4, topological domain 2, signal peptide 1, chain 1, short sequence motif 1, compositionally biased region 1, modified residue 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

showing 30 of 36 structures by resolution:

PDB	Title	Method	Resolution (Å)
2FCW	Structure of a Complex Between the Pair of the LDL Receptor Ligand-Binding Modules 3-4 …	X-RAY DIFFRACTION	1.26
3SO6	Crystal structure of the LDL receptor tail in complex with autosomal recessive …	X-RAY DIFFRACTION	1.37
1IJQ	Crystal Structure of the LDL Receptor YWTD-EGF Domain Pair	X-RAY DIFFRACTION	1.5
1AJJ	LDL RECEPTOR LIGAND-BINDING MODULE 5, CALCIUM-COORDINATING	X-RAY DIFFRACTION	1.7
5OYL	VSV G CR2	X-RAY DIFFRACTION	2.25
2W2N	WT PCSK9-deltaC bound to EGF-A H306Y mutant of LDLR	X-RAY DIFFRACTION	2.3
2W2Q	PCSK9-deltaC D374H mutant bound to WT EGF-A of LDLR	X-RAY DIFFRACTION	2.33
2W2M	WT PCSK9-DELTAC BOUND TO WT EGF-A OF LDLR	X-RAY DIFFRACTION	2.4
3BPS	PCSK9:EGF-A complex	X-RAY DIFFRACTION	2.41
4NE9	PCSK9 in complex with LDLR peptide	X-RAY DIFFRACTION	2.6
2W2O	PCSK9-deltaC D374Y mutant bound to WT EGF-A of LDLR	X-RAY DIFFRACTION	2.62
2W2P	PCSK9-deltaC D374A mutant bound to WT EGF-A of LDLR	X-RAY DIFFRACTION	2.62
3GCW	PCSK9:EGFA(H306Y)	X-RAY DIFFRACTION	2.7
3GCX	PCSK9:EGFA (pH 7.4)	X-RAY DIFFRACTION	2.7
3P5B	The structure of the LDLR/PCSK9 complex reveals the receptor in an extended conformation	X-RAY DIFFRACTION	3.3
5OY9	VSV G CR3	X-RAY DIFFRACTION	3.6
1N7D	Extracellular domain of the LDL receptor	X-RAY DIFFRACTION	3.7
9COO	Nanobody 4 bound to Apolipoprotein B 100	ELECTRON MICROSCOPY	3.73
9BDE	Middle Region of Apolipoprotein B 100 bound to Low Density Lipoprotein Receptor	ELECTRON MICROSCOPY	4.18
3P5C	The structure of the LDLR/PCSK9 complex reveals the receptor in an extended conformation	X-RAY DIFFRACTION	4.2
9BD8	ApoB 100 beta barrel bound to LDLR beta propeller	ELECTRON MICROSCOPY	4.8
9BDT	Apolipoprotein B 100 bound to LDL receptor and legobody	ELECTRON MICROSCOPY	5.4
3M0C	The X-ray Crystal Structure of PCSK9 in Complex with the LDL receptor	X-RAY DIFFRACTION	7.01
1D2J	LDL RECEPTOR LIGAND-BINDING MODULE 6	SOLUTION NMR
1F5Y	NMR STRUCTURE OF A CONCATEMER OF THE FIRST AND SECOND LIGAND-BINDING MODULES OF THE HUMAN …	SOLUTION NMR
1F8Z	NMR STRUCTURE OF THE SIXTH LIGAND-BINDING MODULE OF THE LDL RECEPTOR	SOLUTION NMR
1HJ7	NMR study of a pair of LDL receptor Ca2+ binding epidermal growth factor-like domains, 20 …	SOLUTION NMR
1HZ8	SOLUTION STRUCTURE AND BACKBONE DYNAMICS OF A CONCATEMER OF EGF-HOMOLOGY MODULES OF THE …	SOLUTION NMR
1I0U	SOLUTION STRUCTURE AND BACKBONE DYNAMICS OF A CONCATEMER OF EGF-HOMOLOGY MODULES OF THE …	SOLUTION NMR
1LDL	THREE-DIMENSIONAL STRUCTURE OF A CYSTEINE-RICH REPEAT FROM THE LOW-DENSITY LIPOPROTEIN …	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01130-F1	75.81	0.29

Human Protein Atlas

Protein class: Metabolic proteins, Predicted membrane proteins, Predicted intracellular proteins, Plasma proteins, Disease related genes, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of lipid/glycolipid metabolism

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IH approved · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1)

Type	Positions
Phosphothreonine	724

Disulfide bonds (30)

Type	Positions
Disulfide bond	27–39, 34–52, 46–63, 68–82, 75–95, 89–104, 109–121, 116–134, 128–143, 148–160, 155–173, 167–184, 197–209, 204–222, 216–231, 236–248, 243–261, 255–270, 276–289, 284–302, 296–313, 318–329, 325–338, 340–352, 358–368, 364–377, 379–392, 667–681, 677–696, 698–711

Glycosylation sites (5)

Type	Positions
N-linked (glcnac…) asparagine	97, 156, 272, 515, 657

Mutagenesis-validated functional residues (17)

Position	Phenotype
165	partial loss of binding to getah virus e2-e1 spike glycoproteins.
168	partial loss of binding to getah virus e2-e1 spike glycoproteins.
175	partial loss of binding to getah virus e2-e1 spike glycoproteins.
208	partial loss of binding to getah virus e2-e1 spike glycoproteins.
214	partial loss of binding to getah virus e2-e1 spike glycoproteins.
217	partial loss of binding to getah virus e2-e1 spike glycoproteins.
224	partial loss of binding to getah virus e2-e1 spike glycoproteins.
811	no change. no change; when associated with r-816 and r-830. insensitive to mylip-triggered degradation; when associated with r-816; r-830 …
816	no change. no change; when associated with r-830. no change; when associated with r-811 and r-830. insensitive to mylip-triggered …
821	3-fold decreased affinity for ldlrap1.
821	10-fold decreased affinity for ldlrap1.
828	abolishes interaction with arrb2.
829	decreased affinity for ldlrap1.
830	no change. no change; when associated with r-816. no change; when associated with r-811 and r-816. insensitive to mylip-triggered …
839	no change. insensitive to mylip-triggered degradation; when associated with r-830. insensitive to mylip-triggered degradation; when …
854	no effect on receptor internalization.
854	enhances interaction with arrb2 and receptor internalization.

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 15; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

15 pathways:

ID	Pathway	Evidence
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis	curated
R-HSA-8856828	Clathrin-mediated endocytosis	curated
R-HSA-8964038	LDL clearance	curated
R-HSA-8964026	Chylomicron clearance	electronic
R-HSA-199991	Membrane Trafficking	—
R-HSA-1430728	Metabolism	—
R-HSA-6806667	Metabolism of fat-soluble vitamins	—
R-HSA-196854	Metabolism of vitamins and cofactors	—
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance	—
R-HSA-8964043	Plasma lipoprotein clearance	—
R-HSA-975634	Retinoid metabolism and transport	electronic
R-HSA-9709957	Sensory Perception	—
R-HSA-382551	Transport of small molecules	—
R-HSA-5653656	Vesicle-mediated transport	—
R-HSA-2187338	Visual phototransduction	—

MSigDB gene sets: 691 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_CELLULAR_RESPONSE_TO_LIPOPROTEIN_PARTICLE_STIMULUS, GOBP_MEMORY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_DIGESTION, MODULE_52, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, GOBP_COGNITION, TSENG_IRS1_TARGETS_UP, GOBP_BEHAVIOR, GOBP_REGULATION_OF_TRIGLYCERIDE_METABOLIC_PROCESS

GO Biological Process (42): retinoid metabolic process (GO:0001523), negative regulation of receptor recycling (GO:0001920), lipid metabolic process (GO:0006629), endocytosis (GO:0006897), receptor-mediated endocytosis (GO:0006898), phagocytosis (GO:0006909), long-term memory (GO:0007616), cholesterol metabolic process (GO:0008203), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), positive regulation of triglyceride biosynthetic process (GO:0010867), regulation of phosphatidylcholine catabolic process (GO:0010899), negative regulation of low-density lipoprotein particle clearance (GO:0010989), phospholipid transport (GO:0015914), intestinal cholesterol absorption (GO:0030299), cholesterol transport (GO:0030301), plasma lipoprotein particle clearance (GO:0034381), low-density lipoprotein particle clearance (GO:0034383), high-density lipoprotein particle clearance (GO:0034384), cholesterol homeostasis (GO:0042632), artery morphogenesis (GO:0048844), positive regulation of inflammatory response (GO:0050729), regulation of protein metabolic process (GO:0051246), negative regulation of protein metabolic process (GO:0051248), response to caloric restriction (GO:0061771), negative regulation of astrocyte activation (GO:0061889), cholesterol import (GO:0070508), cellular response to fatty acid (GO:0071398), cellular response to low-density lipoprotein particle stimulus (GO:0071404), receptor-mediated endocytosis involved in cholesterol transport (GO:0090118), regulation of cholesterol metabolic process (GO:0090181), amyloid-beta clearance (GO:0097242), amyloid-beta clearance by cellular catabolic process (GO:0150094), negative regulation of microglial cell activation (GO:1903979), positive regulation of lysosomal protein catabolic process (GO:1905167), negative regulation of amyloid fibril formation (GO:1905907), lipid transport (GO:0006869), steroid metabolic process (GO:0008202), negative regulation of macromolecule metabolic process (GO:0010605), symbiont entry into host cell (GO:0046718), negative regulation of multicellular organismal process (GO:0051241), establishment of localization in cell (GO:0051649)

GO Molecular Function (13): amyloid-beta binding (GO:0001540), virus receptor activity (GO:0001618), protease binding (GO:0002020), low-density lipoprotein particle receptor activity (GO:0005041), calcium ion binding (GO:0005509), low-density lipoprotein particle binding (GO:0030169), very-low-density lipoprotein particle receptor activity (GO:0030229), clathrin heavy chain binding (GO:0032050), identical protein binding (GO:0042802), molecular adaptor activity (GO:0060090), lipoprotein particle binding (GO:0071813), protein binding (GO:0005515), protein-containing complex binding (GO:0044877)

GO Cellular Component (21): lysosome (GO:0005764), early endosome (GO:0005769), late endosome (GO:0005770), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), endosome membrane (GO:0010008), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), clathrin-coated endocytic vesicle membrane (GO:0030669), low-density lipoprotein particle (GO:0034362), endolysosome membrane (GO:0036020), somatodendritic compartment (GO:0036477), signaling receptor complex (GO:0043235), apical part of cell (GO:0045177), sorting endosome (GO:0097443), PCSK9-LDLR complex (GO:1990666), endosome (GO:0005768), endomembrane system (GO:0012505)

Reactome top-level categories

11 top-level categories:

Category	Pathways
Plasma lipoprotein clearance	2
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
Visual phototransduction	1
Metabolism of fat-soluble vitamins	1
Transport of small molecules	1
Metabolism	1
Vesicle-mediated transport	1
Sensory Perception	1
Metabolism of vitamins and cofactors	1
Plasma lipoprotein assembly, remodeling, and clearance	1

GO top-level categories

showing 60 of 78 GO namespaces:

Category	Terms
endosome	4
cellular anatomical structure	4
binding	3
endomembrane system	3
endocytosis	2
gene expression	2
regulation of gene expression	2
plasma lipoprotein particle clearance	2
lipoprotein particle receptor activity	2
membrane	2
protein-containing complex	2
diterpenoid metabolic process	1
receptor recycling	1
regulation of receptor recycling	1
negative regulation of macromolecule metabolic process	1
negative regulation of signaling	1
primary metabolic process	1
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
vesicle-mediated transport	1
memory	1
sterol metabolic process	1
secondary alcohol metabolic process	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
regulation of triglyceride biosynthetic process	1
triglyceride biosynthetic process	1
positive regulation of lipid biosynthetic process	1
positive regulation of triglyceride metabolic process	1
phosphatidylcholine catabolic process	1
regulation of phospholipid catabolic process	1
regulation of phosphatidylcholine metabolic process	1
negative regulation of lipoprotein particle clearance	1
regulation of low-density lipoprotein particle clearance	1
low-density lipoprotein particle clearance	1
lipid transport	1
organophosphate ester transport	1
lipid digestion	1
intestinal lipid absorption	1
sterol transport	1
receptor-mediated endocytosis	1
multicellular organismal process	1
plasma lipoprotein particle disassembly	1
regulation of plasma lipoprotein particle levels	1
low-density lipoprotein particle disassembly	1
sterol homeostasis	1
peptide binding	1
symbiont entry into host cell	1
exogenous protein binding	1
enzyme binding	1
low-density lipoprotein particle binding	1
metal ion binding	1
lipoprotein particle binding	1
very-low-density lipoprotein particle binding	1
clathrin binding	1
protein binding	1
molecular_function	1
protein-lipid complex binding	1
lytic vacuole	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 28 of 76 annotations. The rest are phylogenetic / computational / electronic (IEA).

28 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to low-density lipoprotein particle stimulus	BP	mutant phenotype
cholesterol homeostasis	BP	mutant phenotype
cholesterol import	BP	mutant phenotype
cholesterol transport	BP	mutant phenotype
intestinal cholesterol absorption	BP	mutant phenotype
long-term memory	BP	genetic interaction
low-density lipoprotein particle clearance	BP	mutant phenotype
negative regulation of low-density lipoprotein particle clearance	BP	direct assay
negative regulation of receptor recycling	BP	direct assay
receptor-mediated endocytosis involved in cholesterol transport	BP	mutant phenotype
regulation of protein metabolic process	BP	genetic interaction
response to caloric restriction	BP	genetic interaction
Golgi apparatus	CC	direct assay
PCSK9-LDLR complex	CC	direct assay
cell surface	CC	direct assay
clathrin-coated pit	CC	direct assay
early endosome	CC	direct assay
external side of plasma membrane	CC	direct assay
late endosome	CC	direct assay
lysosome	CC	direct assay
membrane	CC	high-throughput assay
signaling receptor complex	CC	direct assay
identical protein binding	MF	physical interaction
low-density lipoprotein particle binding	MF	mutant phenotype
low-density lipoprotein particle receptor activity	MF	direct assay
molecular adaptor activity	MF	experiment
protease binding	MF	physical interaction
very-low-density lipoprotein particle receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 3,275 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LDLR	APOB	P04114	959
LDLR	APOE	P02649	953
LDLR	PCSK9	Q8NBP7	940
LDLR	HMGCR	P04035	898
LDLR	CETP	P11597	875
LDLR	SCARB1	Q8WTV0	867
LDLR	SREBF2	Q12772	867
LDLR	ABCA1	O95477	864
LDLR	APOA1	P02647	863
LDLR	CYP7A1	P22680	830
LDLR	LDLRAP1	Q5SW96	830
LDLR	SCARB2	Q14108	829
LDLR	ABCG1	P45844	825
LDLR	MYLIP	Q8WY64	824
LDLR	APOC3	P02656	823

IntAct

Human interaction partners of LDLR in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

18 partners by confidence:

Partner	Interaction type	MIscore	Records
LRPAP1	direct interaction	0.740	2
PCSK9	direct interaction	0.720	13
APOE	direct interaction	0.710	4
APOH	direct interaction	0.620	3
APOB	direct interaction	0.560	4
MTIF3	physical association	0.560	3
TLE5	physical association	0.560	3
S	physical association	0.540	2
WNT7A	association	0.530	2
FLT1	colocalization	0.460	2
CREBBP	acetylation reaction	0.440	1
LDLRAP1	direct interaction	0.440	1
PDIA3	disulfide bond	0.440	1
HSPA5	physical association	0.400	1
MMP2	physical association	0.400	1
MAP4	physical association	0.370	1
CBR3	association	0.350	1
KATNBL1	association	0.350	1

BioGRID (505 interactions; top human partners by supporting records): MYLIP (Affinity Capture-Western; 7 records), B3GNT2 (Affinity Capture-MS; 3 records), EGFR (Proximity Label-MS; 3 records), GINM1 (Affinity Capture-MS; 3 records), HSPA5 (Negative Genetic; 3 records), LRPAP1 (Affinity Capture-MS; 3 records), PRG2 (Affinity Capture-MS; 3 records), ZFP41 (Affinity Capture-MS; 3 records), AGO2 (Positive Genetic; 2 records), DAB1 (Two-hybrid; 2 records), DLK2 (Affinity Capture-MS; 2 records), EGFL6 (Affinity Capture-MS; 2 records), FAM19A3 (Affinity Capture-MS; 2 records), FASN (Negative Genetic; 2 records), FCGRT (Affinity Capture-MS; 2 records)

SIGNOR signaling

5 signaling interactions:

A	Effect	B	Mechanism
SREBF2	“up-regulates quantity by expression”	LDLR	“transcriptional regulation”
HNF4A	“up-regulates quantity by expression”	LDLR	“transcriptional regulation”
porfimer	“up-regulates activity”	LDLR	“chemical activation”
MYLIP	“down-regulates quantity by destabilization”	LDLR	ubiquitination
APOB	up-regulates	LDLR	binding

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
★ CAP1-LDLR-PCSK9 complex	3	CAP1, LDLR, PCSK9
★ LDLR-PCSK9 complex	2	LDLR, PCSK9

Disease & clinical

Genetic variants

Variant evidence for LDLR: 4,904 ClinVar records (1,877 pathogenic / likely pathogenic); 567 ClinGen expert-panel interpretations; 6 PharmGKB clinical annotations; 194 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

4,904 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1236
Likely pathogenic	641
Uncertain significance	1210
Likely benign	882
Benign	85

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 1,877 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
161271	NM_000527.5(LDLR):c.1775G>A (p.Gly592Glu)	Pathogenic	reviewed by expert panel	54
161287	NM_000527.5(LDLR):c.798T>A (p.Asp266Glu)	Pathogenic	reviewed by expert panel	51
183106	NM_000527.5(LDLR):c.1027G>A (p.Gly343Ser)	Pathogenic	reviewed by expert panel	48
3736	NM_000527.4(LDLR):c.313+1G>A	Pathogenic	reviewed by expert panel	45
3694	NM_000527.5(LDLR):c.1285G>A (p.Val429Met)	Pathogenic	reviewed by expert panel	43
226304	NM_000527.5(LDLR):c.81C>G (p.Cys27Trp)	Pathogenic	reviewed by expert panel	39
183092	NM_000527.5(LDLR):c.662A>G (p.Asp221Gly)	Pathogenic	reviewed by expert panel	38
3695	NM_000527.5(LDLR):c.1291G>A (p.Ala431Thr)	Pathogenic	reviewed by expert panel	37
161284	NM_000527.5(LDLR):c.1444G>A (p.Asp482Asn)	Pathogenic	reviewed by expert panel	37
226333	NM_000527.5(LDLR):c.682G>T (p.Glu228Ter)	Pathogenic	reviewed by expert panel	37
200921	NM_000527.5(LDLR):c.1747C>T (p.His583Tyr)	Pathogenic	reviewed by expert panel	36
226342	NM_000527.5(LDLR):c.1048C>T (p.Arg350Ter)	Pathogenic	reviewed by expert panel	36
3690	NM_000527.5(LDLR):c.681C>G (p.Asp227Glu)	Pathogenic	reviewed by expert panel	35
3691	NM_000527.5(LDLR):c.682G>A (p.Glu228Lys)	Pathogenic	reviewed by expert panel	35
226379	NM_000527.5(LDLR):c.1897C>T (p.Arg633Cys)	Pathogenic	reviewed by expert panel	35

Per-variant reference — Sugi Variant

Explore LDLR’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

ClinGen expert-panel interpretations (567)

Expert ACMG interpretations from Familial Hypercholesterolemia VCEP for hypercholesterolemia, familial — a higher-authority tier than individual ClinVar submissions.

Assertion	Variants
Pathogenic	78
Likely Pathogenic	137
Uncertain Significance	314
Likely Benign	20
Benign	18

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 1,076):

Position(s)	Effect	Δscore	Sites
19:11089616–11089617	donor_loss	1.0000	4
19:11100221–11100222	acceptor_loss	1.0000	6
19:11100325	donor_gain	1.0000
19:11102662–11102663	acceptor_loss	1.0000	6
19:11105592	donor_gain	1.0000
19:11106563–11106564	acceptor_loss	1.0000	4
19:11106688	donor_loss	1.0000
19:11107380–11107381	acceptor_gain	1.0000	2
19:11107389	acceptor_gain	1.0000
19:11107390–11107391	acceptor_loss	1.0000	5

AlphaMissense

1,845 missense substitutions predicted likely pathogenic (of 5,750 scored), across 451 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D227	8	0.994	0.998
D178	8	0.992	0.999
D100	8	0.991	0.998
D139	8	0.991	0.998
D266	8	0.991	0.997
D307	8	0.990	0.998
D482	8	0.990	0.998
D57	8	0.988	0.998
D579	8	0.988	0.996
D168	8	0.971	0.999
D217	8	0.971	0.998
D133	8	0.967	0.995
D221	8	0.965	0.991
D172	8	0.964	0.991
D94	8	0.960	0.989
D224	8	0.957	0.992
D136	8	0.953	0.989
D492	8	0.951	0.992
D622	8	0.950	0.991
D304	8	0.949	0.990

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Pancreatic Adenocarcinoma (TCGA)	unfavorable	9.21e-05

Disease associations

OMIM: gene MIM:606945 | disease phenotypes: MIM:143890, MIM:300749, MIM:144010, MIM:125853, MIM:603813, MIM:617347

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
hypercholesterolemia, familial, 1	Definitive	Autosomal dominant	4
homozygous familial hypercholesterolemia	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
hypercholesterolemia, familial, 1	Definitive	SD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (13 panels, 13 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

13 panels:

Panel	Rating
Additional findings health related	green
Additional findings health related - CNV analysis adults	green
Additional findings health related - CNV analysis children	green
Additional findings health related - adults	green
Additional findings health related - children	green
Familial hypercholesterolaemia	green
Familial hypercholesterolaemia (GMS)	green
Hypotonic infant	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Paediatric disorders	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green

Mondo (8): familial hypercholesterolemia (MONDO:0005439), hypercholesterolemia, familial, 1 (MONDO:0007750), homozygous familial hypercholesterolemia (MONDO:0018328), syndromic X-linked intellectual disability Najm type (MONDO:0010417), hypercholesterolemia, autosomal dominant, type B (MONDO:0007751), type 2 diabetes mellitus (MONDO:0005148), hypercholesterolemia, familial, 4 (MONDO:0011374), hyperlipoproteinemia type 3 (MONDO:0018473)

Orphanet (3): Homozygous familial hypercholesterolemia (Orphanet:391665), X-linked intellectual disability, Najm type (Orphanet:163937), Dysbetalipoproteinemia (Orphanet:412)

HPO phenotypes

37 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000799	Renal steatosis
HP:0000822	Hypertension
HP:0000991	Xanthomatosis
HP:0001084	Corneal arcus
HP:0001114	Xanthelasma
HP:0001138	Optic neuropathy
HP:0001397	Hepatic steatosis
HP:0001645	Sudden cardiac death
HP:0001653	Mitral regurgitation
HP:0001658	Myocardial infarction
HP:0001677	Coronary artery atherosclerosis
HP:0001681	Angina pectoris
HP:0001920	Renal artery stenosis
HP:0002094	Dyspnea
HP:0002829	Arthralgia
HP:0003077	Hyperlipidemia
HP:0003124	Hypercholesterolemia
HP:0003141	Elevated circulating LDL-C concentration
HP:0004381	Supravalvular aortic stenosis
HP:0004416	Precocious atherosclerosis
HP:0004950	Peripheral arterial stenosis
HP:0004963	Calcification of the aorta
HP:0005162	Abnormal left ventricular function
HP:0005177	Premature arteriosclerosis
HP:0005181	Premature coronary artery atherosclerosis
HP:0006693	Myocardial steatosis
HP:0007201	Cerebral artery atherosclerosis
HP:0010874	Tendon xanthomatosis
HP:0012373	Abnormal eye physiology
HP:0012397	Aortic atherosclerotic lesion
HP:0012638	Abnormal nervous system physiology
HP:0030148	Heart murmur
HP:0030882	Coronary artery aneurysm
HP:0100261	Abnormal tendon morphology
HP:3000062	Abnormal internal carotid artery morphology

GWAS associations

showing 30 of 194 associations:

Study	Trait	p-value
GCST008079_66	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2e-273
GCST002222_36	LDL cholesterol	4e-262
GCST008078_76	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	5e-226
GCST008079_3	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	5e-213
GCST002221_62	Cholesterol, total	5e-202
GCST008078_140	LDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2e-193
GCST008086_66	LDL cholesterol levels in current drinkers	4e-193
GCST008086_51	LDL cholesterol levels in current drinkers	2e-172
GCST002898_4	LDL cholesterol	7e-142
GCST009366_38	LDL cholesterol levels x long total sleep time interaction (2df test)	7e-129
GCST008077_86	LDL cholesterol levels	1e-119
GCST000759_4	LDL cholesterol	4e-117
GCST007931_82	Medication use (HMG CoA reductase inhibitors)	8e-116
GCST002220_1	LDL cholesterol	3e-115
GCST002896_6	Cholesterol, total	2e-113
GCST009365_7	LDL cholesterol levels x short total sleep time interaction (2df test)	4e-112
GCST011347_11	Low density lipoprotein cholesterol levels	1e-100
GCST000760_6	Cholesterol, total	7e-97
GCST008077_2	LDL cholesterol levels	1e-96
GCST010243_200	Apolipoprotein B levels	2e-96
GCST010245_144	LDL cholesterol levels	4e-89
GCST011346_17	Total cholesterol levels	3e-76
GCST000134_4	LDL cholesterol	2e-51
GCST006034_28	Total cholesterol levels	8e-49
GCST005194_121	Coronary artery disease	5e-41
GCST005196_140	Coronary artery disease	5e-41
GCST006004_20	Low density lipoprotein cholesterol levels	4e-40
GCST009366_39	LDL cholesterol levels x long total sleep time interaction (2df test)	1e-35
GCST010866_9	Coronary artery disease	9e-34
GCST009366_41	LDL cholesterol levels x long total sleep time interaction (2df test)	1e-33

EFO canonical traits (from GWAS)

20 canonical traits:

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004529	lipid measurement
EFO:0004746	lipoprotein-associated phospholipase A(2) measurement
EFO:0004723	coronary artery calcification
EFO:0004458	C-reactive protein measurement
EFO:0005843	cortisol measurement
EFO:0007796	parental longevity
EFO:0009783	carotid atherosclerosis
EFO:0009925	Antithrombotic agent use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0007013	aspirin use measurement
EFO:0004329	alcohol drinking
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0010343	cholesteryl ester 18:0 measurement
EFO:0007804	LDL cholesterol change measurement
EFO:0004615	apolipoprotein B measurement
EFO:0009762	healthspan
EFO:0006925	lipoprotein A measurement

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
D003924	Diabetes Mellitus, Type 2	C18.452.394.750.149; C19.246.300
D000090542	Homozygous Familial Hypercholesterolemia	C16.320.565.398.481.500; C18.452.584.500.500.644.475.500; C18.452.584.563.481.500; C18.452.648.398.481.500
C567466	Mental Retardation And Microcephaly With Pontine And Cerebellar Hypoplasia *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3311 (SINGLE PROTEIN), CHEMBL4523996 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 39,362 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL255863	NILOTINIB	4	39,362

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

6 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs14158	Efficacy	3	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin	Chronic hepatitis C virus infection;HIV infectious disease
rs1433099	Efficacy	3	pravastatin	Vascular Diseases
rs2738466	Efficacy	3	pravastatin	Vascular Diseases
rs5925	Efficacy	3	lovastatin
rs688	Efficacy	3	atenolol	Hypertension
rs688	Efficacy	3	lovastatin

PharmGKB variants

5 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs688	LDLR	3	2.75	2	atenolol;lovastatin
rs5925	LDLR	3	2.75	1	lovastatin
rs14158	LDLR	3	2.00	1	peginterferon alfa-2a;peginterferon alfa-2b;ribavirin
rs1433099	LDLR	3	0.00	1	pravastatin
rs2738466	LDLR	3	0.00	1	pravastatin

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

5 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs14158	peginterferon alfa-2a, peginterferon alfa-2b, ribavirin	Efficacy	Genotype GG is associated with increased response to peginterferon alfa-2a, peginterferon alfa-2b and ribavirin in people with Hepatitis C, Chronic and HIV Infections as compared to genotypes AA + AG.	PMID:21572301
rs6511720		Other	Allele T is associated with baseline LDL cholesterol in people with Vascular Diseases.	PMID:21977987
rs2738466	pravastatin	Efficacy	Allele G is associated with increased risk of Coronary Disease when treated with pravastatin in men.	PMID:18261733
rs688	lovastatin	Efficacy	Genotype TT is associated with increased response to lovastatin as compared to genotype CT.	PMID:16103896
rs5925	lovastatin	Efficacy	Genotype CC is associated with increased response to lovastatin as compared to genotype CT.	PMID:16103896

Binding affinities (BindingDB)

390 measured of 399 human assays (399 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-[(8S,14S,17S,20S,23S,26S,29R,32S)-32-(4-aminobutyl)-41-fluoro-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8,29-dimethyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	KI	1.5 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
4-[(8S,14S,17S,20S,23S,26S,29R,32S)-20-(carboxymethyl)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-17-(1H-imidazol-5-ylmethyl)-14-[(4-methoxyphenyl)methyl]-8,29-dimethyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-32-yl]butyl-trimethylazanium	KI	9.5 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
(5R,8S,14S,17S,20S,26S,29S,32R,35S)-35-(4-aminobutyl)-44-fluoro-26,29-bis[(5-fluoro-1H-indol-3-yl)methyl]-17-[(1R)-1-hydroxyethyl]-14-[(4-hydroxyphenyl)methyl]-8,32-dimethyl-7,13,16,19,25,28,31,34,37-nonaoxo-3,40-dithia-6,12,15,18,24,27,30,33,36-nonazatetracyclo[40.3.1.08,12.020,24]hexatetraconta-1(45),42(46),43-triene-5-carboxamide	KI	11 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-32-[4-[3-[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]ethoxy]propanoylamino]butyl]-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	KI	11 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
(5R,8S,14S,17S,20S,26S,29S,35S)-35-(4-aminobutyl)-26,29-bis[(5-fluoro-1H-indol-3-yl)methyl]-17-[(1R)-1-hydroxyethyl]-14-[(4-hydroxyphenyl)methyl]-8-methyl-7,13,16,19,25,28,31,34,37-nonaoxo-3,40-dithia-6,12,15,18,24,27,30,33,36-nonazatetracyclo[40.3.1.08,12.020,24]hexatetraconta-1(45),42(46),43-triene-5-carboxamide	KI	12 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-32-(3-aminopropyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	KI	14 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
(1S,4S,7S,13S,31S,34R,37S,46E,52S)-52-[(5-fluoro-1H-indol-3-yl)methyl]-4-[(1R)-1-methoxyethyl]-7-[(4-methoxyphenyl)methyl]-13,31,34,50-tetramethyl-44-oxa-18,26-dithia-3,6,9,15,30,33,36,50,53-nonazapentacyclo[35.12.5.120,24.139,43.09,13]hexapentaconta-20,22,24(56),39(55),40,42,46-heptaene-2,5,8,14,29,32,35,51,54-nonone	KI	41 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
(5R,8S,14S,20S,26S,29S,32R,35S)-35-(4-aminobutyl)-26,29-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-8,17,17,32-tetramethyl-7,13,16,19,25,28,31,34,37-nonaoxo-3,40-dithia-6,12,15,18,24,27,30,33,36-nonazatetracyclo[40.3.1.08,12.020,24]hexatetraconta-1(45),42(46),43-triene-5-carboxamide	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
(5R,8S,14S,17S,20S,23S,26S,29R,32S)-32-[(1R)-1-methoxyethyl]-14,17,23,26-tetrakis[(4-methoxyphenyl)methyl]-20,29-bis(2-methylpropyl)-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-triene-5-carboxamide	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
(5R,8S,14S,17S,20S,23S,26S,29R,32S)-17,32-bis[(1R)-1-methoxyethyl]-14,23,26-tris[(4-methoxyphenyl)methyl]-8,21-dimethyl-20,29-bis(2-methylpropyl)-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-triene-5-carboxamide	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
(5R,8S,14S,17S,20S,23S,26S,29R,32S)-17-[(1R)-1-methoxyethyl]-14,23,26,32-tetrakis[(4-methoxyphenyl)methyl]-8,21,27-trimethyl-20,29-bis(2-methylpropyl)-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-triene-5-carboxamide	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
(5R,8S,14S,17S,20S,26S,29S,32R,35S)-17-[(1R)-1-methoxyethyl]-14-[(4-methoxyphenyl)methyl]-27,33-dimethyl-26-[(1-methylindol-3-yl)methyl]-32-(2-methylpropyl)-29-(naphthalen-2-ylmethyl)-7,13,16,19,25,28,31,34,37-nonaoxo-35-propyl-3,40-dithia-6,12,15,18,24,27,30,33,36-nonazatetracyclo[40.3.1.08,12.020,24]hexatetraconta-1(45),42(46),43-triene-5-carboxamide	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
(5R,8S,14S,17S,20S,26S,29S,32R,35S)-17-[(1R)-1-methoxyethyl]-14-[(4-methoxyphenyl)methyl]-18,33-dimethyl-26-[(1-methylindol-3-yl)methyl]-32-(2-methylpropyl)-29-(naphthalen-2-ylmethyl)-7,13,16,19,25,28,31,34,37-nonaoxo-35-propyl-3,40-dithia-6,12,15,18,24,27,30,33,36-nonazatetracyclo[40.3.1.08,12.020,24]hexatetraconta-1(45),42(46),43-triene-5-carboxamide	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
(5R,8S,14S,18R,21S,27S,30S,36S)-36-(4-aminobutyl)-27,30-bis[(5-fluoro-1H-indol-3-yl)methyl]-18-[(1R)-1-hydroxyethyl]-14-[(4-hydroxyphenyl)methyl]-8-methyl-7,13,16,20,26,29,32,35,38-nonaoxo-3,41-dithia-6,12,15,19,25,28,31,34,37-nonazatetracyclo[41.3.1.08,12.021,25]heptatetraconta-1(46),43(47),44-triene-5-carboxamide	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
(5R,8S,14S,17S,20S,26S,29S,32R,35S)-35-(4-aminobutyl)-26,29-bis[(5-fluoro-1H-indol-3-yl)methyl]-17-[(1R)-1-hydroxyethyl]-14-[(4-methoxyphenyl)methyl]-8,32-dimethyl-7,13,16,19,25,28,31,34,37-nonaoxo-3,40-dithia-6,12,15,18,24,27,30,33,36-nonazatetracyclo[40.3.1.08,12.020,24]hexatetraconta-1(45),42(46),43-triene-5-carboxamide	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
(5R,8S,14S,17S,20S,26S,29S,32R,35S)-35-(4-aminobutyl)-26,29-bis[(5-fluoro-1H-indol-3-yl)methyl]-17-[(1R)-1-hydroxyethyl]-14-[(4-methoxyphenyl)methyl]-8,32-dimethyl-7,13,16,19,25,28,31,34,37-nonaoxo-3,40-dithia-6,12,15,18,24,27,30,33,36,44-decazatetracyclo[40.3.1.08,12.020,24]hexatetraconta-1(45),42(46),43-triene-5-carboxamide	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
(5R,8S,14S,17S,20S,26S,29S,32R,35S)-35-(4-aminobutyl)-26,29-bis[(5-fluoro-1H-indol-3-yl)methyl]-17-[(1R)-1-hydroxyethyl]-14-[(4-methoxyphenyl)methyl]-8,32-dimethyl-7,13,16,19,25,28,31,34,37-nonaoxo-3,40-dithia-6,12,15,18,24,27,30,33,36,46-decazatetracyclo[40.3.1.08,12.020,24]hexatetraconta-1(45),42(46),43-triene-5-carboxamide	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
(3S,6S,12S,15S,18S,20S,24S,27S,30R,33S,36S)-36-acetamido-33-(4-aminobutyl)-20-fluoro-24,27-bis[(5-fluoro-1H-indol-3-yl)methyl]-15-[(1R)-1-hydroxyethyl]-12-[(4-methoxyphenyl)methyl]-6,30-dimethyl-5,11,14,17,23,26,29,32,35,38-decaoxo-4,10,13,16,22,25,28,31,34,39-decazatetracyclo[39.2.2.06,10.018,22]pentatetraconta-1(44),41(45),42-triene-3-carboxamide	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
(3S,6S,12S,15S,18S,20S,24S,27S,30R,33S,36S)-36-acetamido-33-(4-aminobutyl)-20-fluoro-24,27-bis[(5-fluoro-1H-indol-3-yl)methyl]-15-[(1R)-1-hydroxyethyl]-12-[(4-methoxyphenyl)methyl]-6,30-dimethyl-5,11,14,17,23,26,29,32,35,38-decaoxo-42-oxa-4,10,13,16,22,25,28,31,34,39-decazatetracyclo[41.2.2.06,10.018,22]heptatetraconta-1(46),43(47),44-triene-3-carboxamide	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
(8R,11S,14R,17S,20S,24S,26S,29S,32S,38S,41S)-8-acetamido-11-(4-aminobutyl)-24-fluoro-17,20-bis[(5-fluoro-1H-indol-3-yl)methyl]-29-[(1S)-1-hydroxyethyl]-32-[(4-methoxyphenyl)methyl]-14,38-dimethyl-9,12,15,18,21,27,30,33,39-nonaoxo-2,3,4,10,13,16,19,22,28,31,34,40-dodecazapentacyclo[41.2.2.12,5.022,26.034,38]octatetraconta-1(46),3,5(48),43(47),44-pentaene-41-carboxamide	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(5R,8S,14S,17S,20S,23S,26S,32S,35R)-35-[[(2S)-2-[[(2S)-2-acetamido-3-(1H-imidazol-5-yl)propanoyl]-methylamino]-3-(4-fluorophenyl)propanoyl]amino]-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-21-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(3S,6S,12S,15S,18S,21S,24S,30S)-30-(4-aminobutyl)-3-carbamoyl-21,24-bis[(5-fluoro-1H-indol-3-yl)methyl]-12-[(4-hydroxyphenyl)methyl]-15-(1H-imidazol-5-ylmethyl)-5,11,14,17,20,23,26,29,32-nonaoxo-4,10,13,16,19,22,25,28,31,36,37,38-dodecazatricyclo[34.2.1.06,10]nonatriaconta-1(39),37-dien-18-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(4S,7S,13S,16S,19S,22S,25S,31S)-31-(4-aminobutyl)-4-carbamoyl-22,25-bis[(5-fluoro-1H-indol-3-yl)methyl]-13-[(4-hydroxyphenyl)methyl]-16-(1H-imidazol-5-ylmethyl)-6,12,15,18,21,24,27,30,33-nonaoxo-5,11,14,17,20,23,26,29,32,38,39,40-dodecazatricyclo[36.2.1.07,11]hentetraconta-1(41),39-dien-19-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(8S,14S,17S,20S,23S,26S,29R,32S)-32-(4-aminobutyl)-26-benzhydryl-23-[(5-fluoro-1H-indol-3-yl)methyl]-17-(4H-imidazol-5-ylmethyl)-14-[(4-methoxyphenyl)methyl]-8,29-dimethyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(8S,14S,17S,20S,23S,26S,29R,32S)-32-(4-aminobutyl)-23-[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-26-(1H-indol-3-ylmethyl)-8,15,27,29-tetramethyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(5R,8S,14S,17S,20S,23S,26S)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(imidazolidin-4-ylmethyl)-8-methyl-7,13,16,19,22,25,28,31,34-nonaoxospiro[3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-triene-32,1’-cyclopropane]-20-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(5R,8S,10S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-4-ylmethyl)-7,13,16,19,22,25,28,31,34-nonaoxo-10-phenyl-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(5R,8S,10S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-7,13,16,19,22,25,28,31,34-nonaoxo-10-(trifluoromethyl)-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(5R,8S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-17-(imidazolidin-4-ylmethyl)-14,14-dimethyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(4S,7S,13S,16S,19S,22S,25S,31S,34S)-34-acetamido-4-carbamoyl-22,25-bis[(5-fluoro-1H-indol-3-yl)methyl]-13-[(4-hydroxyphenyl)methyl]-16-(1H-imidazol-5-ylmethyl)-7,31-dimethyl-6,12,15,18,21,24,27,30,33-nonaoxo-5,11,14,17,20,23,26,29,32,39,40,41-dodecazatricyclo[37.2.1.07,11]dotetraconta-1(42),40-dien-19-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(6S,9S,15S,18S,21S,24S,27S,33R)-33-acetamido-6-carbamoyl-24,27-bis[(5-fluoro-1H-indol-3-yl)methyl]-15-[(4-hydroxyphenyl)methyl]-18-(1H-imidazol-5-ylmethyl)-9-methyl-8,14,17,20,23,26,29,32-octaoxo-1,7,13,16,19,22,25,28,31,36,37-undecazatricyclo[33.2.1.09,13]octatriaconta-35(38),36-dien-21-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(5R,8R,14S,17S,20S,23S,26S,32S)-32-(3-aminopropyl)-5-carbamoyl-14-[[4-(cyclohexylmethoxy)phenyl]methyl]-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-17-(1H-imidazol-5-ylmethyl)-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,15,18,21,24,27,30,33-octazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
3-[(8S,14S,17S,20S,23S,26S,29R,32S)-26-[[3-(aminomethyl)phenyl]methyl]-23-[(5-fluoro-1H-indol-3-yl)methyl]-17-[(1R)-1-methoxyethyl]-14-[(4-methoxyphenyl)methyl]-8,29,32-trimethyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]propanoic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
4-[(8S,14S,17R,20S,23S,26S,29R,32S)-26-[[3-(aminomethyl)phenyl]methyl]-23-[(5-fluoro-1H-indol-3-yl)methyl]-17-[(1R)-1-hydroxyethyl]-14-[(4-methoxyphenyl)methyl]-8,29,32-trimethyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]butanoic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-41-hydroxy-14-[(4-hydroxyphenyl)methyl]-17-(imidazolidin-4-ylmethyl)-8-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-17-(imidazolidin-4-ylmethyl)-8-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-14-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(5R,8S,14S,17S,20S,23S,26S,29R,32S)-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8,29-dimethyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]-2-methylpropanoic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(8R,14R,17R,20R,23R,26R,29S,32R)-32-(4-aminobutyl)-29-tert-butyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-17-(imidazolidin-4-ylmethyl)-14-[(4-methoxyphenyl)methyl]-8-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(5R,8S,10S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-10-methylsulfanyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(3S,6S,12S,15S,18S,21S,24S,30S)-30-acetamido-3-carbamoyl-21,24-bis[(5-fluoro-1H-indol-3-yl)methyl]-12-[(4-hydroxyphenyl)methyl]-15-(1H-imidazol-5-ylmethyl)-6-methyl-5,11,14,17,20,23,26,29,36-nonaoxo-38-oxa-4,10,13,16,19,22,25,28,35-nonazatricyclo[37.2.2.06,10]tritetraconta-1(42),39(43),40-trien-18-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(3S,6S,12S,15S,18S,21S,24S,30S)-3-carbamoyl-21,24-bis[(5-fluoro-1H-indol-3-yl)methyl]-12-[(4-hydroxyphenyl)methyl]-15-(1H-imidazol-5-ylmethyl)-6,30-dimethyl-5,11,14,17,20,23,26,29,32,36-decaoxo-4,10,13,16,19,22,25,28,31,37-decazatricyclo[37.2.2.06,10]tritetraconta-1(42),39(43),40-trien-18-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(11S,14R,17S,20S,23S,26S,29S,35S,38S)-11-(4-aminobutyl)-38-carbamoyl-17-[(5-fluoro-1H-indol-3-yl)methyl]-20-[(6-fluoro-1H-indol-3-yl)methyl]-26-(1H-imidazol-5-ylmethyl)-29-[(4-methoxyphenyl)methyl]-14,35-dimethyl-9,12,15,18,21,24,27,30,36-nonaoxo-2,3,4,10,13,16,19,22,25,28,31,37-dodecazatetracyclo[38.2.2.12,5.031,35]pentatetraconta-1(43),3,5(45),40(44),41-pentaen-23-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(3S,6S,12S,15S,18S,21S,24S,30S)-3-carbamoyl-21,24-bis[(5-fluoro-1H-indol-3-yl)methyl]-12-[(4-hydroxyphenyl)methyl]-15-(1H-imidazol-5-ylmethyl)-6,30-dimethyl-5,11,14,17,20,23,26,29,32,37-decaoxo-4,10,13,16,19,22,25,28,31,38-decazatricyclo[38.2.2.06,10]tetratetraconta-1(43),40(44),41-trien-18-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(8S,11S,14R,17S,20S,23S,26S,29S,35S,38S)-8-acetamido-11-(4-aminobutyl)-38-carbamoyl-17,20-bis[(5-fluoro-1H-indol-3-yl)methyl]-26-(1H-imidazol-5-ylmethyl)-29-[(4-methoxyphenyl)methyl]-14,35-dimethyl-9,12,15,18,21,24,27,30,36-nonaoxo-2,3,4,10,13,16,19,22,25,28,31,37-dodecazatetracyclo[38.2.2.12,5.031,35]pentatetraconta-1(43),3,5(45),40(44),41-pentaen-23-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(5R,8S,14S,17S,20S,23S,26S,29R,32S)-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(imidazolidin-4-ylmethyl)-8-methyl-29-(2-methylpropyl)-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-32-(2-hydroxypropan-2-yl)-17-(imidazolidin-4-ylmethyl)-8-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-5-carbamoyl-8-ethyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
3-[(8S,14S,17S,20S,22S,26S,29S,32R,35S)-22-amino-26,29-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-methoxyphenyl)methyl]-8,32,35-trimethyl-7,13,16,19,25,28,31,34,37-nonaoxo-3,40-dithia-6,12,15,18,24,27,30,33,36-nonazatetracyclo[40.2.2.08,12.020,24]hexatetraconta-1(45),42(46),43-trien-17-yl]propanoic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition
2-[(8S,14S,17S,20S,23S,26S,29R,32S)-32-(4-aminobutyl)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8,15,29-trimethyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]-2-methylpropanoic acid	IC50	50 nM	US-11530244: Cyclic polypeptides for PCSK9 inhibition

ChEMBL bioactivities

594 potent at pChembl≥5 of 728 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.70	IC50	2	nM	CHEMBL5278292
8.51	IC50	3.1	nM	CHEMBL5268810
8.15	IC50	7	nM	CHEMBL5418494
8.05	IC50	9	nM	CHEMBL5409584
7.85	Ki	14	nM	CHEMBL4789480
7.75	Ki	17.6	nM	CHEMBL4776000
7.63	Ki	23.3	nM	CHEMBL4754486
7.62	Ki	23.9	nM	CHEMBL4795153
7.58	Ki	26.6	nM	CHEMBL4743963
7.57	Ki	26.9	nM	CHEMBL4764247
7.36	Ki	43.5	nM	CHEMBL4789838
7.33	Ki	47.1	nM	CHEMBL4740764
7.32	Ki	48.1	nM	CHEMBL4799936
7.30	IC50	50	nM	CHEMBL5802613
7.30	IC50	50	nM	CHEMBL5780071
7.30	IC50	50	nM	CHEMBL5996876
7.30	IC50	50	nM	CHEMBL6003304
7.30	IC50	50	nM	CHEMBL5956074
7.30	IC50	50	nM	CHEMBL5756628
7.30	IC50	50	nM	CHEMBL6040707
7.30	IC50	50	nM	CHEMBL6039902
7.30	IC50	50	nM	CHEMBL5763767
7.30	IC50	50	nM	CHEMBL5932491
7.30	IC50	50	nM	CHEMBL5743013
7.30	IC50	50	nM	CHEMBL5882670
7.30	IC50	50	nM	CHEMBL5788292
7.30	IC50	50	nM	CHEMBL6021487
7.30	IC50	50	nM	CHEMBL5835110
7.30	IC50	50	nM	CHEMBL6044373
7.30	IC50	50	nM	CHEMBL5902402
7.30	IC50	50	nM	CHEMBL5767193
7.30	IC50	50	nM	CHEMBL5836575
7.30	IC50	50	nM	CHEMBL5926165
7.30	IC50	50	nM	CHEMBL5906583
7.30	IC50	50	nM	CHEMBL5753404
7.30	IC50	50	nM	CHEMBL6044476
7.30	IC50	50	nM	CHEMBL4759663
7.30	IC50	50	nM	CHEMBL5876842
7.30	IC50	50	nM	CHEMBL5827405
7.30	IC50	50	nM	CHEMBL5779731
7.30	IC50	50	nM	CHEMBL5856574
7.30	IC50	50	nM	CHEMBL5815822
7.30	IC50	50	nM	CHEMBL5808401
7.30	IC50	50	nM	CHEMBL5783539
7.30	IC50	50	nM	CHEMBL5910433
7.30	IC50	50	nM	CHEMBL6002292
7.30	IC50	50	nM	CHEMBL5910875
7.30	IC50	50	nM	CHEMBL5758016
7.30	IC50	50	nM	CHEMBL5743459
7.30	IC50	50	nM	CHEMBL5934279

PubChem BioAssay actives

82 with measured affinity, of 362 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-[(3S,6S,12R,15S,21S,24S,27S,30S,33S,36S,39S,42S,45S)-6-benzyl-12-(ethylcarbamoyl)-39,42-bis[(1R)-1-hydroxyethyl]-21,27,28,33,34-pentamethyl-2,5,8,14,20,23,26,29,32,35,38,41,44-tridecaoxo-30,36-bis[(4-phenylphenyl)methyl]-3-propan-2-yl-10-thia-1,4,7,13,19,22,25,28,31,34,37,40,43-tridecazatricyclo[43.3.0.015,19]octatetracontan-24-yl]propanoic acid	1933148: Inhibition of PCSK9-LDLR (unknown origin) protein-protein interaction	ic50	0.0020	uM
(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-1-[(2R)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S,3S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S,3R)-2-[(2-aminoacetyl)amino]-3-hydroxybutanoyl]amino]-4-oxobutanoyl]amino]-4-carboxybutanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]acetyl]amino]acetyl]amino]-3-sulfanylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-sulfanylpropanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]amino]-3-methylpentanoyl]amino]acetyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-carboxybutanoyl]amino]-3-sulfanylpropanoyl]amino]-4-methylpentanoyl]amino]-3-sulfanylpropanoyl]pyrrolidine-2-carbonyl]amino]-3-carboxypropanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-5-oxopentanoyl]amino]-4-methylpentanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-sulfanylpropanoyl]amino]pentanedioic acid	1933140: Inhibition of human PCSK9-LDLR protein-protein interaction using EGF peptide as substrate preincubated for 30 mins followed by LDLR addition and measured after 2 hrs by ELISA	ic50	0.0031	uM
5-[5-[1-(4,4-dimethylpentyl)-5-naphthalen-2-ylimidazol-2-yl]-2-iodoimidazol-1-yl]-N-methylpentan-1-amine	1990773: Inhibition of His-tagged PCSK9 to recombinant LDLR (unknown origin) protein-protein interaction incubated for 2 hrs by fluorescence plate reader analysis	ic50	0.0070	uM
5-[5-[1-(4,4-dimethylpentyl)-5-naphthalen-2-ylimidazol-2-yl]-2-ethynylimidazol-1-yl]-N-methylpentan-1-amine	1990773: Inhibition of His-tagged PCSK9 to recombinant LDLR (unknown origin) protein-protein interaction incubated for 2 hrs by fluorescence plate reader analysis	ic50	0.0090	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0140	uM
2-[(8S,14S,17S,20S,23S,26S,29R,32S)-32-(4-aminobutyl)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-29-propan-2-yl-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0176	uM
2-[(8S,14S,17S,20S,23S,26S,29R,32S)-32-(4-aminobutyl)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8,29-dimethyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0233	uM
(5R,8S,14S,17S,20S,26S,29S,35S)-35-(4-aminobutyl)-26,29-bis[(5-fluoro-1H-indol-3-yl)methyl]-17-[(1R)-1-hydroxyethyl]-14-[(4-hydroxyphenyl)methyl]-8-methyl-7,13,16,19,25,28,31,34,37-nonaoxo-3,40-dithia-6,12,15,18,24,27,30,33,36-nonazatetracyclo[40.3.1.08,12.020,24]hexatetraconta-1(45),42(46),43-triene-5-carboxamide	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0239	uM
2-[(8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0266	uM
2-[(8S,14S,17S,20S,23S,26S,29R,32S)-32-(4-aminobutyl)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-29-[(1S)-1-hydroxyethyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0269	uM
2-[(8S,14S,17S,20S,23S,26S,29R,32S)-32-(4-aminobutyl)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-29-propyl-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0435	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S,35R)-35-acetamido-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0471	uM
2-[(8S,14S,17S,20S,23S,26S,29R,32S)-29-(4-aminobutyl)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8,32-dimethyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0481	uM
2-[(5R,8S,14S,17S,20S,23S,32S)-32-(4-aminobutyl)-5-carbamoyl-23-[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-26-methyl-26-naphthalen-1-yl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0630	uM
2-[(5R,8S,13S,16S,19S,22S,25S,31S)-31-(4-aminobutyl)-5-carbamoyl-22,25-bis[(5-fluoro-1H-indol-3-yl)methyl]-13-[(4-hydroxyphenyl)methyl]-16-(1H-imidazol-5-ylmethyl)-7,12,15,18,21,24,27,30,33-nonaoxo-3,36-dithia-6,11,14,17,20,23,26,29,32-nonazatricyclo[36.3.1.08,11]dotetraconta-1(41),38(42),39-trien-19-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0675	uM
3-isoquinolin-8-yloxy-4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(4-methylpiperazin-1-yl)phenyl]benzamide	1666983: Inhibition of recombinant human His-tagged PCSK9 interaction with recombinant LDLR AB domain (unknown origin) measured after 3 hrs by horseradish peroxidase-coupled TMB substrate based spectrophotometry	ic50	0.0780	uM
2-[(8S,14S,17S,20S,23S,26S,29R,32S)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-32-(4-hydroxybutyl)-17-(1H-imidazol-5-ylmethyl)-14-[(4-methoxyphenyl)methyl]-8,29-dimethyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0789	uM
(5R,8S,14S,17S,20S,26S,29S,35S)-35-(4-aminobutyl)-26,29-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-8,17-dimethyl-7,13,16,19,25,28,31,34,37-nonaoxo-3,40-dithia-6,12,15,18,24,27,30,33,36-nonazatetracyclo[40.3.1.08,12.020,24]hexatetraconta-1(45),42(46),43-triene-5-carboxamide	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0883	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-32-propyl-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.0947	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S,35R)-35-acetamido-32-(4-aminobutyl)-5-carbamoyl-23-[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-26-(1H-indol-3-ylmethyl)-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.1030	uM
2-[(3S,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,39R,42S)-39-[(2-amino-2-oxoethyl)carbamoyl]-33-benzyl-3-(3-carbamimidamidopropyl)-21,24-bis[(1R)-1-hydroxyethyl]-27-(hydroxymethyl)-9,10,15,16-tetramethyl-2,5,8,11,14,17,20,23,26,29,32,35,41-tridecaoxo-12,18-bis[(4-phenylphenyl)methyl]-30-propan-2-yl-37-thia-1,4,7,10,13,16,19,22,25,28,31,34,40-tridecazabicyclo[40.3.0]pentatetracontan-6-yl]acetic acid	1933161: Inhibition of PCSK9-LDLR protein-protein interaction in human HepG2 cells assessed as increase in LDL uptake	ec50	0.1060	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.1100	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-15-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.1120	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-32-(3-aminopropyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.1325	uM
3-[(5R,8S,11S,14S,17S,20S,23S,26S,29S,32S,35S,38R)-38-(2-acetamidohexanoylamino)-35-tert-butyl-5-carbamoyl-8,26-bis[(1R)-1-hydroxyethyl]-14,32-bis[(4-hydroxyphenyl)methyl]-29-(1H-imidazol-5-ylmethyl)-7,10,13,16,19,22,25,28,31,34,37-undecaoxo-11,20-dipropyl-23-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-3,40-dithia-6,9,12,15,18,21,24,27,30,33,36-undecazabicyclo[40.3.1]hexatetraconta-1(45),42(46),43-trien-17-yl]propanoic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.1340	uM
3-[(8S,14S,17S,20S,23S,26S,29R,32S)-20-(carboxymethyl)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-8,29-dimethyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-32-yl]propanoic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.2022	uM
2-[(8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.2520	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-33-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.3420	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-32-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.3920	uM
(5R,8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-20-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-triene-5-carboxamide	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.4270	uM
N-[3-[[(3S)-3-aminopiperidin-1-yl]methyl]-5-(4-methylimidazol-1-yl)phenyl]-3-[[4-(4-fluorophenyl)pyrimidin-2-yl]amino]-4-methylbenzamide	1666983: Inhibition of recombinant human His-tagged PCSK9 interaction with recombinant LDLR AB domain (unknown origin) measured after 3 hrs by horseradish peroxidase-coupled TMB substrate based spectrophotometry	ic50	0.4280	uM
4-methyl-N-[3-(4-methylimidazol-1-yl)-5-piperazin-1-ylphenyl]-3-[(4-phenylpyrimidin-2-yl)amino]benzamide	1666983: Inhibition of recombinant human His-tagged PCSK9 interaction with recombinant LDLR AB domain (unknown origin) measured after 3 hrs by horseradish peroxidase-coupled TMB substrate based spectrophotometry	ic50	0.4910	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.5250	uM
N-[3-[[(3S)-3-aminopiperidin-1-yl]methyl]-5-(4-methylimidazol-1-yl)phenyl]-4-methyl-3-phenoxybenzamide	1666983: Inhibition of recombinant human His-tagged PCSK9 interaction with recombinant LDLR AB domain (unknown origin) measured after 3 hrs by horseradish peroxidase-coupled TMB substrate based spectrophotometry	ic50	0.5370	uM
N-[3-(1,3-benzodioxol-5-ylmethylamino)-4-methylphenyl]-3-cyclohexylpropanamide	102351: Concentration at which one-half of the maximum Low density lipoprotein receptor is upregulated in HepG2 cells	ec50	0.6000	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S)-32-(4-aminobutyl)-5-carbamoyl-23-[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-26-methyl-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.6560	uM
N-[3-[(Z)-2-(1,3-benzodioxol-5-yl)-2-cyanoethenyl]-4-methylphenyl]-3-cyclohexylpropanamide	102351: Concentration at which one-half of the maximum Low density lipoprotein receptor is upregulated in HepG2 cells	ec50	0.7000	uM
3-cyclohexyl-N-[3-(6-hydroxy-1H-benzimidazol-2-yl)-4-methylphenyl]propanamide	102351: Concentration at which one-half of the maximum Low density lipoprotein receptor is upregulated in HepG2 cells	ec50	0.7000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-amino-4-methylpentanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]butanedioic acid	1933148: Inhibition of PCSK9-LDLR (unknown origin) protein-protein interaction	ic50	0.7000	uM
4-methyl-N-[3-(4-methylimidazol-1-yl)-5-[(4-methylpiperazin-1-yl)methyl]phenyl]-3-[(4-phenylpyrimidin-2-yl)amino]benzamide	1666983: Inhibition of recombinant human His-tagged PCSK9 interaction with recombinant LDLR AB domain (unknown origin) measured after 3 hrs by horseradish peroxidase-coupled TMB substrate based spectrophotometry	ic50	0.7140	uM
4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(4-methylpiperazin-1-yl)phenyl]-3-[(4-phenylpyrimidin-2-yl)amino]benzamide	1666983: Inhibition of recombinant human His-tagged PCSK9 interaction with recombinant LDLR AB domain (unknown origin) measured after 3 hrs by horseradish peroxidase-coupled TMB substrate based spectrophotometry	ic50	0.7580	uM
4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(4-methylpiperazin-1-yl)phenyl]-3-phenoxybenzamide	1666983: Inhibition of recombinant human His-tagged PCSK9 interaction with recombinant LDLR AB domain (unknown origin) measured after 3 hrs by horseradish peroxidase-coupled TMB substrate based spectrophotometry	ic50	0.7590	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-acetamido-3-hydroxybutanoyl]amino]-3-methylbutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1933148: Inhibition of PCSK9-LDLR (unknown origin) protein-protein interaction	ic50	0.8000	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S,35R)-35-[[(2S)-2-[[(2S)-2-acetamido-3-(1H-imidazol-5-yl)propanoyl]-methylamino]-3-(4-fluorophenyl)propanoyl]amino]-32-(4-aminobutyl)-5-carbamoyl-23,26-bis[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.9560	uM
2-[(5R,8S,15S,18S,21S,24S,27S,33S)-33-(4-aminobutyl)-5-carbamoyl-24,27-bis[(5-fluoro-1H-indol-3-yl)methyl]-15-[(4-hydroxyphenyl)methyl]-18-(1H-imidazol-5-ylmethyl)-7,14,17,20,23,26,29,32,35-nonaoxo-3,38-dithia-6,13,16,19,22,25,28,31,34-nonazatricyclo[38.3.1.08,13]tetratetraconta-1(43),40(44),41-trien-21-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	0.9690	uM
N-[3-[(Z)-2-cyano-2-pyridin-3-ylethenyl]-4-methylphenyl]-3-cyclohexylpropanamide	102351: Concentration at which one-half of the maximum Low density lipoprotein receptor is upregulated in HepG2 cells	ec50	1.0000	uM
2-[(5R,8S,14S,17S,20S,23S,26S,32S,35R)-35-acetamido-32-(4-aminobutyl)-5-carbamoyl-26-[(5-fluoro-1H-indol-3-yl)methyl]-14-[(4-hydroxyphenyl)methyl]-17-(1H-imidazol-5-ylmethyl)-23-(1H-indol-3-ylmethyl)-7,13,16,19,22,25,28,31,34-nonaoxo-3,37-dithia-6,12,15,18,21,24,27,30,33-nonazatricyclo[37.3.1.08,12]tritetraconta-1(42),39(43),40-trien-20-yl]acetic acid	1700388: Inhibition of avi-tagged-biotinylated human PCSK9 interaction with His-tagged human LDLR EGFa domain by LANCE Ulight Streptavidin based TR-FRET assay	ki	1.0700	uM
5-[5-[1-(cyclohexylmethyl)-5-naphthalen-2-ylimidazol-2-yl]-2-ethynylimidazol-1-yl]-N-methylpentan-1-amine	1990773: Inhibition of His-tagged PCSK9 to recombinant LDLR (unknown origin) protein-protein interaction incubated for 2 hrs by fluorescence plate reader analysis	ic50	1.1800	uM
N-[5-(3-cyclohexylpropanoylamino)-2-methylphenyl]pyridine-3-carboxamide	102351: Concentration at which one-half of the maximum Low density lipoprotein receptor is upregulated in HepG2 cells	ec50	1.2000	uM
N-[3-(1H-benzimidazol-2-yl)-4-methylphenyl]-3-cyclohexylpropanamide	102351: Concentration at which one-half of the maximum Low density lipoprotein receptor is upregulated in HepG2 cells	ec50	1.3000	uM

CTD chemical–gene interactions

227 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Simvastatin	affects expression, increases expression, decreases expression, increases activity, affects response to substance (+3 more)	15
Cyclosporine	affects cotreatment, affects binding, decreases reaction, increases degradation, increases expression	7
fatostatin	increases reaction, increases response to substance, decreases expression	6
bisphenol A	affects expression, decreases expression, increases expression	5
Valproic Acid	affects expression, affects methylation, decreases expression	5
sodium arsenite	decreases expression, increases expression	4
25-hydroxycholesterol	increases cleavage, decreases expression, affects cotreatment, decreases activity, increases activity (+4 more)	3
perfluorooctane sulfonic acid	decreases expression	3
Atorvastatin	increases activity, increases expression	3
Troglitazone	affects binding, decreases expression, increases activity, increases expression	3
Fluvastatin	affects response to substance, affects binding, increases reaction, increases activity, affects cotreatment	3
Acetaminophen	increases expression, affects cotreatment, decreases expression, affects binding, increases reaction (+1 more)	3
Cisplatin	affects cotreatment, increases expression, decreases expression, decreases reaction	3
Curcumin	decreases expression, decreases reaction, increases activity, increases expression	3
Lovastatin	increases activity, increases expression, increases reaction	3
triphenyl phosphate	affects expression, increases expression	2
cobaltous chloride	increases expression, decreases expression	2
perfluorooctanoic acid	decreases expression, increases expression	2
potassium chromate(VI)	decreases expression, affects cotreatment	2
Air Pollutants	decreases expression, increases abundance, increases expression, decreases reaction, affects cotreatment	2
Ethanol	decreases expression, affects cotreatment, increases abundance, decreases reaction	2
Aspirin	increases reaction, affects binding, increases degradation, decreases reaction, increases abundance	2
Benzo(a)pyrene	decreases expression	2
Cholesterol	increases chemical synthesis, increases reaction, increases uptake, affects cotreatment, decreases activity (+1 more)	2
Dexamethasone	affects reaction, decreases expression, increases expression, decreases reaction	2
Estradiol	increases expression	2
Hydrogen Peroxide	increases expression, affects cotreatment	2
Lipopolysaccharides	increases expression, decreases reaction, affects expression, affects response to substance	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2

ChEMBL screening assays

55 unique, capped per target: 54 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2091225	Binding	Displacement of S-tagged Ac-DSGL[CMPRLRGC]cDPR-NH2 from human DsRed2-fused LDLR expressed in CHO cells at 10 uM after 1 hr by FRET assay	Chemical optimization of new ligands of the low-density lipoprotein receptor as potential vectors for central nervous system targeting. — *J Med Chem*
CHEMBL706292	Functional	Capability of derepressing the transcription of Low density lipoprotein receptor promoter in the presence of 25-hydroxycholesterol in CHO cells measured as maximum activity at 20 ug/mL	Synthesis and biological evaluation of a new series of sterols as potential hypocholesterolemic agents. — *J Med Chem*

Cellosaurus cell lines

49 cell lines: 23 finite cell line, 15 induced pluripotent stem cell, 7 cancer cell line, 4 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1V08	GM02000	Finite cell line	Female
CVCL_4N05	GM00700	Finite cell line	Female
CVCL_4N06	GM00701	Finite cell line	Female
CVCL_4N13	GM01448	Transformed cell line	Female
CVCL_4N16	GM01460	Transformed cell line	Female
CVCL_4N19	GM01915	Finite cell line	Female
CVCL_4N35	GM03040	Finite cell line	Male
CVCL_4N38	GM03064	Finite cell line	Male
CVCL_4N39	GM03065	Finite cell line	Female
CVCL_7288	GM00483	Finite cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 183 trials:

NCT	Phase	Status	Title
NCT06231459	Phase 4	COMPLETED	Expression of Pro- and Anti-inflammatory Cytokines During Anti-PCSK9 in Familial Hypercholesterolemia
NCT00655265	Phase 4	COMPLETED	A Study of the Safety and Efficacy of Patients With Familial Hypercholesterolaemia Taking Colesevelam as add-on Therapy to Their Existing Medication
NCT00916643	Phase 4	COMPLETED	Low-Density Lipoprotein (LDL) Apheresis Using H.E.L.P. Therapy
NCT03331666	Phase 4	TERMINATED	Impact of LDL-cholesterol Lowering on Platelet Activation
NCT05465278	Phase 4	COMPLETED	Alirocumab and Plaque Burden In Familial Hypercholesterolaemia
NCT00000594	Phase 3	COMPLETED	NHLBI Type II Coronary Intervention Study
NCT00092833	Phase 3	TERMINATED	Investigational Drug in Patients With Hypercholesterolemia or in Patients With Sitosterolemia (0653-026)(COMPLETED)
NCT00134485	Phase 3	COMPLETED	Study To Evaluate The Safety And Efficacy Of Torcetrapib/Atorvastatin In Subjects With Familial Hypercholerolemia
NCT00134511	Phase 3	COMPLETED	Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Patients With Genetic High Cholesterol Disorder
NCT00136981	Phase 3	COMPLETED	Carotid B-Mode Ultrasound Study to Compare Anti-Atherosclerotic Effect of Torcetrpib/Atorvastatin to Atorvastatin Alone.
NCT00384293	Phase 3	TERMINATED	Carotid IMT (Intima Media Thickening) Study (0524A-041)(TERMINATED)
NCT01524289	Phase 3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT00730236	Phase 3	COMPLETED	A Safety and Efficacy Study of AEGR-733 to Treat Homozygous Familial Hypercholesterolemia (FH)
NCT01841684	Phase 3	TERMINATED	Efficacy and Tolerability of Anacetrapib Added to Ongoing Lipid-Lowering Therapy in Adult Participants With Homozygous Familial Hypercholesterolemia (HoFH) (MK-0859-042)
NCT02226198	Phase 3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia
NCT02434497	Phase 3	COMPLETED	A Study to Evaluate the Safety of Rosuvastatin in Children and Adolescents With Homozygous Familial Hypercholesterolemia
NCT02765841	Phase 3	WITHDRAWN	Evaluate the Efficacy and Safety of Lomitapide in Pediatric Patients With Homozygous Familial Hypercholesterolemia on Stable Lipid-lowering Therapy
NCT03156621	Phase 3	COMPLETED	Study in Participants With Homozygous Familial Hypercholesterolemia (HoFH)
NCT03399786	Phase 3	COMPLETED	Efficacy and Safety of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia
NCT03409744	Phase 3	COMPLETED	Evaluate the Long-Term Safety and Efficacy of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia
NCT03814187	Phase 3	COMPLETED	Trial to Assess the Effect of Long Term Dosing of Inclisiran in Subjects With High CV Risk and Elevated LDL-C
NCT03851705	Phase 3	COMPLETED	A Study of Inclisiran in Participants With Homozygous Familial Hypercholesterolemia (HoFH)
NCT04034485	Phase 3	COMPLETED	Phase 3 Study to Evaluate the Efficacy and Safety of LIB003 With Evolocumab in HoFH
NCT04233918	Phase 3	COMPLETED	Evaluate the Efficacy and Safety of Evinacumab in Pediatric Patients With Homozygous Familial Hypercholesterolemia
NCT05611528	Phase 3	COMPLETED	Safety and Effectiveness of Evinacumab for the Treatment of Homozygous Familial Hypercholesterolemia
NCT05682378	Phase 3	RECRUITING	Long-term Safety and Tolerability of Inclisiran in Participants With HeFH or HoFH Who Have Completed the Pediatric ORION-16, ORION-13, ORION-20, or ORION-19 Studies
NCT06712771	Phase 3	ACTIVE_NOT_RECRUITING	A Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of VSA003 in Chinese HoFH Patients
NCT06723652	Phase 3	COMPLETED	A Multicenter, Randomized, Double-blind, Placebo-controlled Phase III Clinical Study Evaluating the Efficacy and Safety of SHR-1918 in Patients With Homozygous Familial Hypercholesterolemia
NCT07037771	Phase 3	ACTIVE_NOT_RECRUITING	A Phase 3 Study of Zodasiran in Adolescent and Adult Subjects With Homozygous Familial Hypercholesterolemia (YOSEMITE)
NCT07473843	Phase 3	NOT_YET_RECRUITING	Study of Zodasiran in Adolescent Participants With Homozygous Familial Hypercholesterolemia
NCT00355615	Phase 3	COMPLETED	PLUTO: Pediatric Lipid-redUction Trial of rOsuvastatin
NCT00552097	Phase 3	COMPLETED	Effect of Ezetimibe Plus Simvastatin Versus Simvastatin Alone on Atherosclerosis in the Carotid Artery (ENHANCE)(P02578)
NCT00607373	Phase 3	COMPLETED	Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia
NCT00694109	Phase 3	COMPLETED	An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia
NCT00827606	Phase 3	COMPLETED	Atorvastatin Three Year Pediatric Study
NCT00943306	Phase 3	COMPLETED	Long Term, Follow-on Study of Lomitapide in Patients With Homozygous Familial Hypercholesterolemia
NCT01813006	Phase 3	COMPLETED	Effect of Omega-3 Fatty Acid on Endothelial Function
NCT02624869	Phase 3	COMPLETED	Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Children With Inherited Elevated Low-density Lipoprotein Cholesterol (Familial Hypercholesterolemia)
NCT02748057	Phase 3	COMPLETED	A Clinical Trial to Assess the Long Term Safety and Tolerability of MK-0653H in Japanese Participants With Hypercholesterolemia (MK-0653H-833)
NCT03884452	Phase 3	COMPLETED	Ezetimibe (SCH 58235) Taken With Either Atorvastatin or Simvastatin in Participants With Familial Hypercholesterolemia (MK-0653-018)
NCT04798430	Phase 3	ENROLLING_BY_INVITATION	Long-term Efficacy and Safety of OLE LIB003 in HoFH, HeFH, and High-risk CVD Patients Requiring Further LDL-C Reduction
NCT05142722	Phase 3	COMPLETED	Randomized Study to Evaluate the Effect of Obicetrapib on Top of Maximum Tolerated Lipid-Modifying Therapies
NCT05238519	Phase 3	COMPLETED	Improved Diagnosis of Familial Hypercholesterolemia Across the Northland (ID-FH)
NCT05425745	Phase 3	COMPLETED	Evaluate the Effect of Obicetrapib in Patients With HeFH on Top of Maximum Tolerated Lipid-Modifying Therapies.
NCT05952856	Phase 3	COMPLETED	A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-013) CORALreef Lipids
NCT05952869	Phase 3	COMPLETED	A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Heterozygous Familial Hypercholesterolemia (MK-0616-017/CORALreef HeFH)
NCT06005597	Phase 3	COMPLETED	Study of Obicetrapib & Ezetimibe Fixed Dose Combination on Top of Maximum Tolerated Lipid-Modifying Therapies
NCT00280995	Phase 2	COMPLETED	Dose-escalating Safety Study of ISIS 301012 in Homozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT00281008	Phase 2	COMPLETED	Study of ISIS 301012 (Mipomersen) in Heterozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT01375751	Phase 2	COMPLETED	Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
NCT01412034	Phase 2	COMPLETED	Effect of CER-001 on Plaque Volume in Homozygous Familial Hypercholesterolemia (HoFH) Subjects
NCT01556906	Phase 2	COMPLETED	Safety, Tolerability and Efficacy of Microsomal Triglyceride Protein (MTP) Inhibitor
NCT02265952	Phase 2	COMPLETED	Study of REGN1500 in Participants With Homozygous Familial Hypercholesterolemia (HoFH)
NCT02472535	Phase 2	COMPLETED	Study to Evaluate the Effects of MBX-8025 in Patients With HoFH
NCT02963311	Phase 2	COMPLETED	A Study of ALN-PCSSC in Participants With Homozygous Familial Hypercholesterolemia (HoFH)
NCT03455777	Phase 2	WITHDRAWN	Study of AKCEA-ANGPTL3-LRX (ISIS 703802) in Patients With Homozygous Familial Hypercholesterolemia (HoFH)
NCT03933293	Phase 2	COMPLETED	A Study to Evaluate the Safety and Efficacy of the PCSK9 Inhibitor AK102 in Patients With HoFH
NCT05217667	Phase 2	TERMINATED	Study of ARO-ANG3 in Participants With Homozygous Familial Hypercholesterolemia (HOFH)
NCT06009393	Phase 2	COMPLETED	Evaluate the Efficacy and Safety of SHR-1918 in Patients With Homozygous Familial Hypercholesterolemia
NCT07133815	Phase 2	NOT_YET_RECRUITING	Evaluate the Long-term Efficacy and Safety of SHR-1918 in Patients With Homozygous Familial Hypercholesterolemia

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for LDLR across ~30M SureChEMBL compounds — explore on Sugi Predict.