LNPEP

Summary

LNPEP (leucyl and cystinyl aminopeptidase, HGNC:6656) is a protein-coding gene on chromosome 5q15, encoding Leucyl-cystinyl aminopeptidase (Q9UIQ6). Release of an N-terminal amino acid, cleaves before cysteine, leucine as well as other amino acids.

This gene encodes a zinc-dependent aminopeptidase that cleaves vasopressin, oxytocin, lys-bradykinin, met-enkephalin, dynorphin A and other peptide hormones. The protein can be secreted in maternal serum, reside in intracellular vesicles with the insulin-responsive glucose transporter GLUT4, or form a type II integral membrane glycoprotein. The protein catalyzes the final step in the conversion of angiotensinogen to angiotensin IV (AT4) and is also a receptor for AT4. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 4012 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 131 total
• Druggable target: yes
• MANE Select transcript: NM_005575

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6656
Approved symbol	LNPEP
Name	leucyl and cystinyl aminopeptidase
Location	5q15
Locus type	gene with protein product
Status	Approved
Aliases	CAP, PLAP, P-LAP, IRAP
Ensembl gene	ENSG00000113441
Ensembl biotype	protein_coding
OMIM	151300
Entrez	4012

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000231368, ENST00000395770, ENST00000395784, ENST00000473914, ENST00000474122, ENST00000882743, ENST00000930837

RefSeq mRNA: 2 — MANE Select: NM_005575 NM_005575, NM_175920

CCDS: CCDS4087, CCDS43346

Canonical transcript exons

ENST00000231368 — 18 exons

Exon	Start	End
ENSE00001083383	97014939	97015095
ENSE00001175110	97027733	97027814
ENSE00001175116	97026617	97026757
ENSE00001175127	97024521	97024682
ENSE00001175135	97022300	97022484
ENSE00001175147	97013648	97013831
ENSE00001175157	97006427	97006515
ENSE00001175167	97006073	97006233
ENSE00001175186	96996390	96996503
ENSE00001175193	96993817	96993971
ENSE00001175196	96993015	96993135
ENSE00001175204	96986539	96986670
ENSE00001175211	96985080	96985218
ENSE00001826672	96936080	96936174
ENSE00001886292	97028402	97037513
ENSE00003468453	97003415	97003546
ENSE00003475848	96998014	96998145
ENSE00003637141	96979138	96979978

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 98.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.7370 / max 399.1578, expressed in 1811 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57723	25.3081	1795
57719	6.2946	1611
57717	0.7271	283
57722	0.6212	360
57721	0.5585	293
57715	0.4334	202
57718	0.2636	132
57727	0.1944	65
57724	0.0858	18
57728	0.0779	3

Top tissues by expression

297 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
visceral pleura	UBERON:0002401	98.50	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.46	gold quality
tibia	UBERON:0000979	98.39	gold quality
parietal pleura	UBERON:0002400	98.36	gold quality
epithelium of nasopharynx	UBERON:0001951	97.87	gold quality
nasopharynx	UBERON:0001728	97.85	gold quality
superficial temporal artery	UBERON:0001614	97.60	gold quality
germinal epithelium of ovary	UBERON:0001304	97.40	gold quality
saphenous vein	UBERON:0007318	97.40	gold quality
middle temporal gyrus	UBERON:0002771	97.17	gold quality
trabecular bone tissue	UBERON:0002483	97.16	gold quality
upper leg skin	UBERON:0004262	97.09	gold quality
gingival epithelium	UBERON:0001949	97.00	gold quality
skin of hip	UBERON:0001554	96.98	gold quality
pleura	UBERON:0000977	96.91	gold quality
seminal vesicle	UBERON:0000998	96.72	gold quality
urethra	UBERON:0000057	96.64	gold quality
superior surface of tongue	UBERON:0007371	96.58	gold quality
penis	UBERON:0000989	96.49	gold quality
gingiva	UBERON:0001828	96.48	gold quality
oral cavity	UBERON:0000167	96.41	gold quality
endothelial cell	CL:0000115	96.28	gold quality
cardia of stomach	UBERON:0001162	96.17	gold quality
biceps brachii	UBERON:0001507	96.14	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.14	gold quality
esophagus squamous epithelium	UBERON:0006920	96.13	gold quality
synovial joint	UBERON:0002217	96.01	gold quality
substantia nigra pars compacta	UBERON:0001965	95.95	gold quality
cauda epididymis	UBERON:0004360	95.95	gold quality
pylorus	UBERON:0001166	95.88	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, IKZF1, IKZF2, IKZF3, IKZF4, IKZF5, TFAP2A

miRNA regulators (miRDB)

73 targeting LNPEP, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-3529-3P	99.90	73.55	3045
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-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-3133	99.81	70.92	3506

Literature-anchored findings (GeneRIF, showing 39)

• Identification of a tankyrase-binding motif in this protein (PMID:12080061)
• Interleukin-1beta stimulates expression in BeWo choriocarcinoma cells (PMID:12569180)
• The expression of IRAP/P-LAP is not limited to fat and muscle cells, and the subcellular distribution of IRAP/P-LAP is regulated by different peptide hormones and exercise. (PMID:12700100)
• Of a range of peptides tested, only vasopressin, oxytocin, and met-enkephalin were rapidly cleaved by IRAP. We propose that the physiological effects of AT4 ligands result from inhibition of IRAP cleavage of neuropeptides involved in memory processing (PMID:12871575)
• Placental leucine aminopeptidase/oxytocinase gene regulation by activator protein-2 in BeWo cell model of human trophoblast differentiation. (PMID:14527672)
• This review characterizes insulin-regulated IRAP in muscle and fat cells and discusses how impaired IRAP action may play a role in the development of complications in type 2 diabetes. (PMID:15187412)
• P-LAP/OTase is type II integral membrane protein, which is converted to soluble form existing in maternal serum by metalloproteases. It may be involved in maintaining pregnancy homeostasis via metabolizing peptides such as OT & vasopressin[review] (PMID:15894523)
• oxytocinase subfamily of M1 aminopeptidases play important roles in the maintenance of homeostasis including maintenance of normal pregnancy, memory retention, blood pressure regulation and antigen presentation [review] (PMID:16054015)
• RCAS1 and CAP may play a role in the downregulation of the maternal immune response during pregnancy and may participate in the initiation of the labor (PMID:16113565)
• no significant increase of oxytocinase plasma level in first trimester spontaneous abortions (PMID:16136012)
• insulin-stimulated IRAP translocation remained intact despite substantial GLUT4 knockdown (PMID:17059388)
• In addition to its capacity to degrade a range of peptides, placental-leucine aminopeptidase (P-LAP) has novel functions that impact on normal cells and neoplastic cells. (PMID:17373876)
• Substrate degradation studies using vasopressin & Leu-enkephalin showed that replacement of G428 by either D, E or Q selectively abolished the catalysis of Leu-enkephalin, while [A429G]IRAP & [N432A]IRAP mutants were incapable of cleaving both substrates (PMID:17391061)
• fluorimetrically analysis of membrane-bound and soluble Cystinyl aminopeptidase activity in the three main renal cancers: clear cell (CCRCC), papillary (PRCC), and chromophobe (ChRCC) renal cell carcinomas (PMID:17692401)
• Data show that placental leucine aminopeptidase (P-LAP) plays important roles in the regulation of blood pressure under both the physiological and pathological conditions. (PMID:17999179)
• Insulin-regulated aminopeptidase (IRAP)/AT4 receptors are involved in neither the regulation of RBF or CBF nor in the handling of renal sodium. (PMID:18398343)
• study identifies smooth muscle cell alpha actin positive ACE2 and AT4R in blood vessels as well as in angiogenic vessels, indicating a possible role for these enzymes in pathological disease (PMID:18502721)
• Triton-slowed APN as well as PLAP is present in the serum of pregnant women. (PMID:18996364)
• distinct biological effects of Angiotensin II 3-8 fragment, denoted as Angiotensin IV, and high affinity Ang IV binding to the AT(4) receptor. [review] (PMID:19071192)
• study found a role for peptide trimming by IRAP in cross-presentation; in dendritic cells, IRAP was localized to a Rab14+ endosomal storage compartment in which it interacted with MHC class I molecules (PMID:19498108)
• The probable involvement of P-LAP in trophoblast invasion and development of preeclampsia. (PMID:20150869)
• Expression of AT4R was increased in term placentae, with a significant reduction in pre-eclampsia placentae. (PMID:20304486)
• Although PLAP has the necessary enzymatic properties to participate in generating or destroying major histocompatibility class I-presented peptides, its trimming behavior during antigen processing is distinct from that of ERAP1. (PMID:20592285)
• S1 specificity pocket of the aminopeptidases that generate antigenic peptides. (PMID:21314638)
• The genetic variation in LNPEP (vasopressinase) is associated with 28-day mortality in septic shock and is associated with biologic effects on vasopressin clearance and serum sodium regulation (PMID:21330387)
• investigation of domain structure of IRAP; catalytic domains; inhibitor-binding domains; zinc binding sites (PMID:21348480)
• Activities of aminopeptidases N and B and insulin-regulated aminopeptidase could be useful non-invasive biomarkers of Alzheimer’s disease from the earliest stages. (PMID:23500679)
• An association between maternal common polymorphisms in LNPEP and susceptibility to preterm birth was observed. (PMID:23889750)
• We identified the missense variant rs2303138 (p.Ala763Thr) within the LNPEP gene associated with psoriasis. (PMID:23897274)
• Determined is the crystal structure of human IRAP revealing a closed, four domain arrangement with a large, mostly buried cavity abutting the active site. (PMID:25408552)
• The substrate Angiotensin II, the enzymes aminopeptidases-A, B, M as well as IRAP were detected in the jejunal mucosa. (PMID:26311161)
• Vasopressinase might be a potential early biomarker for acute kidney injury after cardiopulmonary bypass. (PMID:26366890)
• Structural and biological characterization of three low molecular weight aryl sulfonamides: binding modes to human IRAP were explored by docking calculations combined with molecular dynamics simulations and binding affinity estimations using the linear interaction energy method. Two of these drug-like IRAP inhibitors can alter dendritic spine morphology and increase spine density in primary cultures of hippocampal neurons (PMID:27501164)
• The PCR-RFLP is a simple and reliable method that allows a quick genotyping for the rs4869317 SNP of LNPEP gene. (PMID:27834335)
• This study shown that the schizophrenia patients, the numerical density of IRAP-expressing neurons in the paraventricular and the suprachiasmatic nuclei is significantly reduced, which might be associated with the reduction in neurophysin-containing neurons in these nuclei in schizophrenia. (PMID:28035472)
• This study describes a crystal structure of insulin-regulated aminopeptidase in complex with a recently developed bioactive and selective inhibitor at 2.53 A resolution. (PMID:28328206)
• LNPEP expression in the left atrium in mitral regurgitation patients significantly differed from those in aortic valve disease patients and normal controls. (PMID:30581499)
• The role of LNPEP and ANPEP gene polymorphisms in the pathogenesis of pre-eclampsia. (PMID:32619880)
• Cell-Specific and Variant-Linked Alterations in Expression of ERAP1, ERAP2, and LNPEP Aminopeptidases in Psoriasis. (PMID:36716917)

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
danio_rerio	lnpep	ENSDARG00000100394
mus_musculus	Lnpep	ENSMUSG00000023845
rattus_norvegicus	Lnpep	ENSRNOG00000055229
drosophila_melanogaster	CG7653	FBGN0028935
drosophila_melanogaster	CG9806	FBGN0030222
drosophila_melanogaster	CG2111	FBGN0030223
drosophila_melanogaster	CG6071	FBGN0036186
drosophila_melanogaster	CG5849	FBGN0038897
drosophila_melanogaster	CG3502	FBGN0046253
drosophila_melanogaster	CG31233	FBGN0051233
drosophila_melanogaster	CG31343	FBGN0051343
drosophila_melanogaster	CG31445	FBGN0051445
drosophila_melanogaster	SP1029	FBGN0263236
drosophila_melanogaster	CG46339	FBGN0285963
caenorhabditis_elegans	F49B2.6	WBGENE00009865
caenorhabditis_elegans		WBGENE00011587
caenorhabditis_elegans		WBGENE00012776

Paralogs (11): TRHDE (ENSG00000072657), LTA4H (ENSG00000111144), ENPEP (ENSG00000138792), NPEPPS (ENSG00000141279), RNPEPL1 (ENSG00000142327), AOPEP (ENSG00000148120), ERAP1 (ENSG00000164307), ERAP2 (ENSG00000164308), ANPEP (ENSG00000166825), LVRN (ENSG00000172901), RNPEP (ENSG00000176393)

Protein

Protein identifiers

Leucyl-cystinyl aminopeptidase — Q9UIQ6 (reviewed: Q9UIQ6)

Alternative names: Insulin-regulated membrane aminopeptidase, Insulin-responsive aminopeptidase, Oxytocinase, Placental leucine aminopeptidase

All UniProt accessions (1): Q9UIQ6

UniProt curated annotations — full annotation on UniProt →

Function. Release of an N-terminal amino acid, cleaves before cysteine, leucine as well as other amino acids. Degrades peptide hormones such as oxytocin, vasopressin and angiotensin III, and plays a role in maintaining homeostasis during pregnancy. May be involved in the inactivation of neuronal peptides in the brain. Cleaves Met-enkephalin and dynorphin. Binds angiotensin IV and may be the angiotensin IV receptor in the brain.

Subunit / interactions. Homodimer. Binds tankyrases 1 and 2.

Subcellular location. Cell membrane Secreted.

Tissue specificity. Highly expressed in placenta, heart, kidney and small intestine. Detected at lower levels in neuronal cells in the brain, in skeletal muscle, spleen, liver, testes and colon.

Post-translational modifications. The pregnancy serum form is derived from the membrane-bound form by proteolytic processing. N-glycosylated.

Cofactor. Binds 1 zinc ion per subunit.

Similarity. Belongs to the peptidase M1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UIQ6-1	1	yes
Q9UIQ6-2	2
Q9UIQ6-3	3

RefSeq proteins (2): NP_005566, NP_787116 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001930	Peptidase_M1	Family
IPR014782	Peptidase_M1_dom	Domain
IPR024571	ERAP1-like_C_dom	Domain
IPR027268	Peptidase_M4/M1_CTD_sf	Homologous_superfamily
IPR034016	M1_APN-typ	Family
IPR042097	Aminopeptidase_N-like_N_sf	Homologous_superfamily
IPR045357	Aminopeptidase_N-like_N	Domain
IPR050344	Peptidase_M1_aminopeptidases	Family

Pfam: PF01433, PF11838, PF17900

Enzyme classification (BRENDA):

• EC 3.4.11.3 — cystinyl aminopeptidase (BRENDA: 14 organisms, 100 substrates, 297 inhibitors, 49 Km, 3 kcat entries)

Substrate kinetics (BRENDA)

23 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
S-BENZYL-L-CYSTEINE-P-NITROANILIDE	0.0056–0.45	10
L-LEU-2-NAPHTHYLAMIDE	0.045–0.59	7
L-LEUCINE-P-NITROANILIDE	0.23–0.867	5
LEU-4-NITROANILIDE	0.243–0.9148	5
L-LEU-4-NITROANILIDE	0.15–0.25	2
L-LYSINE-P-NITROANILIDE	0.43–3	2
ARG-4-NITROANILIDE	0.529	1
ARGININE-4-METHYLCOUMARIN 7-AMIDE	0.022	1
CYS-4-NITROANILIDE	0.331	1
L-ALA-2-NAPHTHYLAMIDE	0.5	1
L-ALANINE-P-NITROANILIDE	1.43	1
L-ARG-2-NAPHTHYLAMIDE	0.046	1
L-CYSTEINE-NITROANILIDE	0.0225	1
L-METHIONINE-P-NITROANILIDE	0.83	1
L-PHE-7-AMIDO-4-METHYLCOUMARIN	0.11	1

UniProt features (136 total): strand 40, helix 38, glycosylation site 17, turn 9, binding site 5, sequence variant 5, sequence conflict 5, modified residue 4, chain 2, site 2, topological domain 2, splice variant 2, short sequence motif 2, transmembrane region 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
5MJ6	X-RAY DIFFRACTION	2.53
8CGP	X-RAY DIFFRACTION	2.62
7ZYF	X-RAY DIFFRACTION	2.81
4PJ6	X-RAY DIFFRACTION	2.96
4P8Q	X-RAY DIFFRACTION	3.02
8CGW	X-RAY DIFFRACTION	3.03
5JHQ	X-RAY DIFFRACTION	3.2
6YDX	X-RAY DIFFRACTION	3.2
4Z7I	X-RAY DIFFRACTION	3.31
5C97	X-RAY DIFFRACTION	3.37
8P0I	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UIQ6-F1	89.03	0.83

Functional residue map

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

Catalytic / active sites (3): 154–155 (cleavage; to produce pregnancy serum form); 549 (transition state stabilizer); 465 (proton acceptor)

Ligand- & substrate-binding residues (5): 428–432; 464; 468; 487; 295

Post-translational modifications (4): 1, 70, 80, 91

Glycosylation sites (17): 145, 184, 215, 256, 266, 368, 374, 448, 525, 578, 598, 664, 682, 760, 834, 850, 989

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-1236977	Endosomal/Vacuolar pathway
R-HSA-1445148	Translocation of SLC2A4 (GLUT4) to the plasma membrane
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1236975	Antigen processing-Cross presentation
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 208 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_REGULATION_OF_BLOOD_PRESSURE, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_CIRCULATORY_SYSTEM_PROCESS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOMF_METALLOPEPTIDASE_ACTIVITY, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GOCC_VACUOLAR_MEMBRANE, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, NKX25_02, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN, REACTOME_MEMBRANE_TRAFFICKING, GGGTGGRR_PAX4_03, BILD_SRC_ONCOGENIC_SIGNATURE

GO Biological Process (10): protein polyubiquitination (GO:0000209), antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent (GO:0002480), proteolysis (GO:0006508), cell-cell signaling (GO:0007267), female pregnancy (GO:0007565), regulation of blood pressure (GO:0008217), neuropeptide catabolic process (GO:0010813), protein catabolic process (GO:0030163), negative regulation of cold-induced thermogenesis (GO:0120163), antigen processing and presentation of peptide antigen via MHC class I (GO:0002474)

GO Molecular Function (8): aminopeptidase activity (GO:0004177), metallopeptidase activity (GO:0008237), zinc ion binding (GO:0008270), metalloaminopeptidase activity (GO:0070006), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (9): extracellular region (GO:0005576), lysosomal membrane (GO:0005765), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), early endosome lumen (GO:0031905), perinuclear region of cytoplasm (GO:0048471), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Class I MHC mediated antigen processing & presentation	2
Antigen processing-Cross presentation	1
Membrane Trafficking	1
Immune System	1
Vesicle-mediated transport	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
protein metabolic process	2
protein ubiquitination	1
antigen processing and presentation of exogenous peptide antigen via MHC class I	1
cell communication	1
signaling	1
multi-organism reproductive process	1
multi-multicellular organism process	1
blood circulation	1
regulation of biological quality	1
peptide catabolic process	1
macromolecule catabolic process	1
negative regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
antigen processing and presentation of peptide antigen	1
exopeptidase activity	1
peptidase activity	1
transition metal ion binding	1
aminopeptidase activity	1
metalloexopeptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cation binding	1
lysosome	1
lytic vacuole membrane	1
membrane	1
cell periphery	1
vesicle membrane	1
cytoplasmic vesicle	1
early endosome	1
endosome lumen	1
intracellular vesicle	1

Protein interactions and networks

STRING

1805 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LNPEP	SLC2A4	P14672	891
LNPEP	LIX1	Q8N485	866
LNPEP	OXT	P01178	865
LNPEP	INS	P01308	815
LNPEP	CNOT12	Q9C0C2	802
LNPEP	TBC1D4	O60343	792
LNPEP	TNKS	O95271	765
LNPEP	AGT	P01019	728
LNPEP	TERF1	P54274	723
LNPEP	RAB14	P35287	682
LNPEP	VAMP2	P19065	653
LNPEP	TNKS2	Q9H2K2	630
LNPEP	TPP2	P29144	624
LNPEP	SORT1	Q99523	611
LNPEP	NUMA1	Q14980	592

IntAct

127 interactions, top by confidence:

A	B	Type	Score
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
LNPEP	CANX	psi-mi:“MI:0914”(association)	0.640
TNKS2	LNPEP	psi-mi:“MI:0915”(physical association)	0.610
TNKS2	LNPEP	psi-mi:“MI:0407”(direct interaction)	0.610
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
TCF4	LNPEP	psi-mi:“MI:0915”(physical association)	0.560
LNPEP	REL	psi-mi:“MI:0915”(physical association)	0.560
LNPEP	FATE1	psi-mi:“MI:0915”(physical association)	0.560
REL	LNPEP	psi-mi:“MI:0915”(physical association)	0.560
LNPEP	TCF4	psi-mi:“MI:0915”(physical association)	0.560
FATE1	LNPEP	psi-mi:“MI:0915”(physical association)	0.560
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
CLGN	NPC1	psi-mi:“MI:0914”(association)	0.530
PNOC	CETN3	psi-mi:“MI:0914”(association)	0.530
TNF	B4GALT5	psi-mi:“MI:0914”(association)	0.530
SCGB1D4	EGFR	psi-mi:“MI:0914”(association)	0.530
TMEM267	ECPAS	psi-mi:“MI:0914”(association)	0.530
DLK1	SCAMP3	psi-mi:“MI:0914”(association)	0.530
LGALS1	LAMA5	psi-mi:“MI:0914”(association)	0.530
HLA-DRA	ENTPD6	psi-mi:“MI:0914”(association)	0.530

BioGRID (306): REL (Two-hybrid), TCF4 (Two-hybrid), FATE1 (Two-hybrid), LNPEP (Affinity Capture-MS), LNPEP (Affinity Capture-MS), LNPEP (Affinity Capture-MS), LNPEP (Affinity Capture-MS), LNPEP (Affinity Capture-MS), LNPEP (Affinity Capture-MS), LNPEP (Affinity Capture-MS), LNPEP (Affinity Capture-MS), LNPEP (Affinity Capture-MS), LNPEP (Affinity Capture-MS), LNPEP (Proximity Label-MS), LNPEP (Proximity Label-MS)

ESM2 similar proteins: A0A6J2ATK2, A5HUI5, A6QPT7, D3UW23, M3XFH7, O57579, O88917, O88923, O94910, O95490, O97817, O97827, O97831, P15144, P15145, P15541, P15684, P16406, P42658, P42659, P46101, P50123, P79098, P79143, P79171, P97449, P97629, Q07075, Q10737, Q22523, Q2KHK3, Q2M2H8, Q32LQ0, Q5RFP3, Q6P179, Q6Q4G3, Q7Q2T8, Q7TT41, Q80TR1, Q80TS3

Diamond homologs: A0A6J2ATK2, A6NEC2, A6QPT7, M3XFH7, O57579, P15144, P15145, P15541, P15684, P46557, P50123, P79098, P79143, P79171, P97449, P97629, Q07075, Q10736, Q10836, Q2KHK3, Q32LQ0, Q5RFP3, Q6P179, Q6Q4G3, Q7Q2T8, Q8C129, Q8K093, Q95334, Q9EQH2, Q9JJ22, Q9UIQ6, Q9UKU6, A5HUI5, D3UW23, O93654, O93655, P0DQU2, P16406, P32454, P37893

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
TFAP2A	“up-regulates quantity by expression”	LNPEP	“transcriptional regulation”
IKZF1	“up-regulates quantity by expression”	LNPEP	“transcriptional regulation”
IKZF2	“up-regulates quantity by expression”	LNPEP	“transcriptional regulation”
IKZF3	“up-regulates quantity by expression”	LNPEP	“transcriptional regulation”
IKZF4	“up-regulates quantity by expression”	LNPEP	“transcriptional regulation”
IKZF5	“up-regulates quantity by expression”	LNPEP	“transcriptional regulation”
LNPEP	“down-regulates quantity by destabilization”	Oxytocin	cleavage

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 159 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
antigen processing and presentation of exogenous peptide antigen via MHC class II	5	20.4×	2e-03
positive regulation of type II interferon production	6	10.1×	6e-03
ERAD pathway	7	9.5×	2e-03
protein transport	12	4.0×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	112
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3307 predictions. Top by Δscore:

Variant	Effect	Δscore
5:96979127:T:A	acceptor_gain	1.0000
5:96979128:G:A	acceptor_gain	1.0000
5:96979133:TTTA:T	acceptor_loss	1.0000
5:96979135:TA:T	acceptor_loss	1.0000
5:96979136:A:AG	acceptor_gain	1.0000
5:96979136:AGATC:A	acceptor_gain	1.0000
5:96979137:G:A	acceptor_loss	1.0000
5:96979137:G:GG	acceptor_gain	1.0000
5:96979137:GATC:G	acceptor_gain	1.0000
5:96979137:GATCG:G	acceptor_gain	1.0000
5:96985182:GGA:G	donor_gain	1.0000
5:96985183:G:T	donor_gain	1.0000
5:96985214:CTAAG:C	donor_loss	1.0000
5:96985215:TAAG:T	donor_loss	1.0000
5:96985216:AAGG:A	donor_loss	1.0000
5:96985218:GGTAC:G	donor_loss	1.0000
5:96985219:G:T	donor_loss	1.0000
5:96985220:T:A	donor_loss	1.0000
5:96986530:T:TA	acceptor_gain	1.0000
5:96986534:TGTAG:T	acceptor_loss	1.0000
5:96986537:A:AG	acceptor_gain	1.0000
5:96986538:G:GG	acceptor_gain	1.0000
5:96986538:GA:G	acceptor_gain	1.0000
5:96986538:GAA:G	acceptor_gain	1.0000
5:96986538:GAAGT:G	acceptor_gain	1.0000
5:96986653:G:GT	donor_gain	1.0000
5:96993011:TTA:T	acceptor_loss	1.0000
5:96993013:A:AG	acceptor_gain	1.0000
5:96993013:AGGTT:A	acceptor_loss	1.0000
5:96993014:G:A	acceptor_loss	1.0000

AlphaMissense

6757 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:96985134:T:G	C305W	0.997
5:96996390:T:A	W470R	0.997
5:96996390:T:C	W470R	0.997
5:97013795:G:C	R728P	0.997
5:96986590:A:C	S351R	0.996
5:96986592:T:A	S351R	0.996
5:96986592:T:G	S351R	0.996
5:96996420:T:A	W480R	0.996
5:96996420:T:C	W480R	0.996
5:96996422:G:C	W480C	0.996
5:96996422:G:T	W480C	0.996
5:96996432:T:A	W484R	0.996
5:96996432:T:C	W484R	0.996
5:97006115:T:A	W610R	0.996
5:97006115:T:C	W610R	0.996
5:96986581:T:C	F348L	0.995
5:96986583:T:A	F348L	0.995
5:96986583:T:G	F348L	0.995
5:96993856:A:T	E431V	0.994
5:97013804:T:C	L731P	0.994
5:96985132:T:C	C305R	0.993
5:96985156:G:C	A313P	0.993
5:96985209:T:A	N330K	0.993
5:96985209:T:G	N330K	0.993
5:96986602:A:C	S355R	0.993
5:96986604:C:A	S355R	0.993
5:96986604:C:G	S355R	0.993
5:96993860:T:A	N432K	0.993
5:96993860:T:G	N432K	0.993
5:96993861:T:A	W433R	0.993

dbSNP variants (sampled 300 via entrez): RS1000017993 (5:97002696 A>G), RS1000060592 (5:97022865 C>T), RS1000100819 (5:96969429 C>G), RS1000157881 (5:96974558 A>C,G), RS1000182073 (5:97004417 C>A,T), RS1000226992 (5:96941860 G>A), RS1000249042 (5:96951443 A>G), RS1000308183 (5:96947854 A>G), RS1000353992 (5:96990523 G>A,C), RS1000359971 (5:96948204 A>G), RS1000421457 (5:96988780 T>C), RS1000446662 (5:96976256 C>G,T), RS1000454520 (5:96936021 C>A,T), RS1000473205 (5:96988499 C>G,T), RS1000485792 (5:96949706 A>C)

Disease associations

OMIM: gene MIM:151300 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001725_70	Inflammatory bowel disease	6.000000e-13
GCST002501_1	Birdshot chorioretinopathy	2.000000e-09
GCST004131_97	Inflammatory bowel disease	1.000000e-10
GCST004132_104	Crohn’s disease	1.000000e-14
GCST005528_16	Juvenile idiopathic arthritis (oligoarticular or rheumatoid factor-negative polyarticular)	7.000000e-09
GCST005529_27	Ankylosing spondylitis	6.000000e-14
GCST005529_28	Ankylosing spondylitis	5.000000e-17
GCST007362_1	Acute anterior uveitis (with or without ankylosing spondylitis)	2.000000e-16
GCST90002389_208	Lymphocyte percentage of white cells	1.000000e-10
GCST90002398_470	Neutrophil count	8.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2693 (SINGLE PROTEIN), CHEMBL3831223 (PROTEIN FAMILY)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — M1: Aminopeptidase N

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
inhibitor 19 [PMID: 21476495]	Inhibition	8.74	pKi
compound 17 [PMID: 23916253]	Inhibition	5.22	pIC50

Binding affinities (BindingDB)

242 measured of 242 human assays (242 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2R,3S)-3-amino-2-[(4-cyclohexyloxy-2-pyridinyl)methyl]-2-hydroxy-3-[4-(4-methylsulfonylphenyl)phenyl]propanoic acid	IC50	0.89 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-[[4-(3,3-dimethylbutoxy)-5-methyl-2-pyridinyl]methyl]-2-hydroxy-5-methylhexanoic acid	IC50	0.94 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-[[4-(4,4-dimethylpiperidin-1-yl)-2-pyridinyl]methyl]-2-hydroxy-5-methylhexanoic acid	IC50	0.95 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-hydroxy-5-methyl-2-[(4-piperidin-1-yl-2-pyridinyl)methyl]hexanoic acid	IC50	1 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-hydroxy-5-methyl-2-[[4-[(2R)-1-phenylpropan-2-yl]oxy-2-pyridinyl]methyl]hexanoic acid	IC50	1.2 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-hydroxy-5-methyl-2-[[4-(4-methylcyclohexyl)oxy-2-pyridinyl]methyl]hexanoic acid	IC50	1.3 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-hydroxy-5-methyl-2-[[4-(1-phenylmethoxycarbonylpiperidin-4-yl)oxy-2-pyridinyl]methyl]hexanoic acid	IC50	1.3 nM	US-10059720: Pyridine derivative
(2R,3R)-3-amino-2-hydroxy-2-[[4-(4-methylcyclohexyl)oxy-2-pyridinyl]methyl]-4-propylsulfanylbutanoic acid	IC50	1.3 nM	US-10059720: Pyridine derivative
(2R,3R)-3-amino-2-hydroxy-2-[[4-(4-methylcyclohexyl)oxy-2-pyridinyl]methyl]-4-methylsulfanylbutanoic acid	IC50	1.4 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-[[1-(2-cyclohexylethyl)imidazo[4,5-c]pyridin-6-yl]methyl]-2-hydroxy-5-methylhexanoic acid	IC50	1.5 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-[[4-(2-bicyclo[2.2.1]heptanyloxy)-2-pyridinyl]methyl]-2-hydroxy-5-methylhexanoic acid	IC50	1.5 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-hydroxy-5-methyl-2-[[4-(2-thiophen-3-ylethoxy)-2-pyridinyl]methyl]hexanoic acid	IC50	1.5 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-[(4-cyclohexyloxy-2-pyridinyl)methyl]-2-hydroxy-3-(4-morpholin-4-ylphenyl)propanoic acid	IC50	1.6 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-hydroxy-5-methyl-2-[[4-(2,2,6,6-tetramethyloxan-4-yl)oxy-2-pyridinyl]methyl]hexanoic acid	IC50	1.6 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-hydroxy-5-methyl-2-[[5-methyl-4-(4-methylcyclohexyl)oxy-2-pyridinyl]methyl]hexanoic acid	IC50	1.6 nM	US-10059720: Pyridine derivative
(2R,3R)-3-amino-2-[[4-(4-cyclopropylbutyl)-5-methyl-2-pyridinyl]methyl]-2-hydroxy-4-methylsulfanylbutanoic acid	IC50	1.6 nM	US-10005762: Pyridine derivatives
(2R,3S)-3-amino-2-[(1-hexylpyrrolo[3,2-c]pyridin-6-yl)methyl]-2-hydroxy-5-methylhexanoic acid	IC50	1.8 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-[(4-cyclohexyloxy-2-pyridinyl)methyl]-2-hydroxy-3-(4-pyridin-3-ylphenyl)propanoic acid	IC50	1.8 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-hydroxy-5-methyl-2-[[4-(1-oxaspiro[4.5]decan-8-yloxy)-2-pyridinyl]methyl]hexanoic acid	IC50	1.8 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-[(4-cyclohexyloxy-2-pyridinyl)methyl]-2-hydroxy-4-(oxan-4-ylidene)butanoic acid	IC50	1.8 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-hydroxy-5-methyl-2-[[5-methyl-4-[(E)-2-phenylethenyl]-2-pyridinyl]methyl]hexanoic acid	IC50	1.8 nM	US-10005762: Pyridine derivatives
(2R,3S)-3-amino-2-[[4-[[(1R,5S)-3-bicyclo[3.1.0]hexanyl]oxy]-2-pyridinyl]methyl]-2-hydroxy-5-methylhexanoic acid	IC50	1.9 nM	US-10059720: Pyridine derivative
(2R,3R)-3-amino-4-ethylsulfanyl-2-hydroxy-2-[[4-(4-methylcyclohexyl)oxy-2-pyridinyl]methyl]butanoic acid	IC50	1.9 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-hydroxy-5-methyl-2-[[4-(4-methylcyclohexyl)oxy-2-pyridinyl]methyl]hexanoic acid	IC50	2 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-[[4-[(2R)-hexan-2-yl]oxy-2-pyridinyl]methyl]-2-hydroxy-5-methylhexanoic acid	IC50	2.1 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-hydroxy-5-methyl-2-[[6-[(1-methylcyclopropyl)methyl]-6,7-dihydro-5H-cyclopenta[c]pyridin-1-yl]methyl]hexanoic acid	IC50	2.1 nM	US-10005762: Pyridine derivatives
(2R,3S)-3-amino-2-[[4-(4-cyclopropylbutyl)-5-methyl-2-pyridinyl]methyl]-2-hydroxy-5-methylhexanoic acid	IC50	2.2 nM	US-10005762: Pyridine derivatives
(2R,3S)-3-amino-2-[(4-cyclohexyloxy-2-pyridinyl)methyl]-2-hydroxy-6-methylheptanoic acid	IC50	2.3 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-[(4-cyclohexyloxy-2-pyridinyl)methyl]-2-hydroxy-8-methoxyoctanoic acid	IC50	2.3 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-[[4-(3-cyclopropylpropyl)-5-methyl-2-pyridinyl]methyl]-2-hydroxy-5-methylhexanoic acid	IC50	2.3 nM	US-10005762: Pyridine derivatives
(2R,3S)-3-amino-2-hydroxy-5-methyl-2-[(4-spiro[2.5]octan-6-yloxy-2-pyridinyl)methyl]hexanoic acid	IC50	2.4 nM	US-10059720: Pyridine derivative
(2R,3R)-3-amino-2-[[2-(2-cyclopropylethyl)furo[3,2-c]pyridin-4-yl]methyl]-2-hydroxy-4-methylsulfanylbutanoic acid	IC50	2.4 nM	US-10023583: Bicyclic pyridine compound
(2R,3S)-3-amino-5-cyclopropyl-2-[[4-(3-cyclopropylpropyl)-5-methyl-2-pyridinyl]methyl]-2-hydroxypentanoic acid	IC50	2.4 nM	US-10005762: Pyridine derivatives
(2R,3S)-3-amino-2-[(4-cyclohexyloxy-2-pyridinyl)methyl]-2-hydroxy-5-methylhexanoic acid	IC50	2.5 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-[(4-cyclohexyloxy-2-pyridinyl)methyl]-2-hydroxy-3-(4-phenylphenyl)propanoic acid	IC50	2.6 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-[(4-cyclohexyloxy-2-pyridinyl)methyl]-2-hydroxy-4-[(5-methyl-2-pyridinyl)oxy]butanoic acid	IC50	2.6 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-hydroxy-2-[[4-(4-hydroxyhexyl)-5-methyl-2-pyridinyl]methyl]-5-methylhexanoic acid	IC50	2.6 nM	US-10005762: Pyridine derivatives
(2R,3S)-3-amino-2-hydroxy-5-methyl-2-[(5-methyl-4-pentyl-2-pyridinyl)methyl]hexanoic acid	IC50	2.6 nM	US-10005762: Pyridine derivatives
(2R,3S)-3-amino-2-[(4-cyclohexyloxy-2-pyridinyl)methyl]-2-hydroxy-4-[4-(methoxymethyl)phenoxy]butanoic acid	IC50	2.7 nM	US-10059720: Pyridine derivative
(2R,3S)-2-[[4-(2-adamantyloxy)-2-pyridinyl]methyl]-3-amino-2-hydroxy-5-methylhexanoic acid	IC50	2.8 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-hydroxy-5-methyl-2-[[4-[2-(1-methylcyclopropyl)ethoxy]-2-pyridinyl]methyl]hexanoic acid	IC50	2.9 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-[[4-(2,3-dihydro-1H-inden-2-yloxy)-2-pyridinyl]methyl]-2-hydroxy-5-methylhexanoic acid	IC50	2.9 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-hydroxy-5,5-dimethyl-2-[[4-(4-methylcyclohexyl)oxy-2-pyridinyl]methyl]hexanoic acid	IC50	2.9 nM	US-10059720: Pyridine derivative
(E,2R,3S)-3-amino-2-[(4-cyclohexyloxy-2-pyridinyl)methyl]-2-hydroxy-5-phenylpent-4-enoic acid	IC50	3 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-hydroxy-5-methyl-2-[[4-[(2R)-4-methylpentan-2-yl]oxy-2-pyridinyl]methyl]hexanoic acid	IC50	3 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-[[4-(2-cyclohexyloxyethoxy)-2-pyridinyl]methyl]-2-hydroxy-5-methylhexanoic acid	IC50	3 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-[(4-hexoxy-2-pyridinyl)methyl]-2-hydroxy-5-methylhexanoic acid	IC50	3 nM	US-10059720: Pyridine derivative
(2R,3S)-3-amino-2-hydroxy-5-methyl-2-[[4-(naphthalen-1-ylmethoxy)-2-pyridinyl]methyl]hexanoic acid	IC50	3.1 nM	US-10059720: Pyridine derivative
(2R,3R)-3-amino-2-[(2-butyl-7-methylfuro[3,2-c]pyridin-4-yl)methyl]-2-hydroxy-4-methylsulfanylbutanoic acid	IC50	3.1 nM	US-10023583: Bicyclic pyridine compound
(2R,3S)-3-amino-2-[[4-(3-cyclopropylpropyl)-5-methyl-2-pyridinyl]methyl]-5-fluoro-2-hydroxy-5-methylhexanoic acid	IC50	3.1 nM	US-10005762: Pyridine derivatives

ChEMBL bioactivities

641 potent at pChembl≥5 of 692 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.05	IC50	0.89	nM	CHEMBL5858644
9.03	IC50	0.94	nM	CHEMBL6013513
9.02	IC50	0.95	nM	CHEMBL6020816
9.00	IC50	1	nM	CHEMBL5847848
8.92	IC50	1.2	nM	CHEMBL5900568
8.89	IC50	1.3	nM	CHEMBL5845804
8.89	IC50	1.3	nM	CHEMBL6046862
8.89	IC50	1.3	nM	CHEMBL5925746
8.85	IC50	1.4	nM	CHEMBL5832194
8.82	IC50	1.5	nM	CHEMBL5983220
8.82	IC50	1.5	nM	CHEMBL5875249
8.82	IC50	1.5	nM	CHEMBL5889833
8.80	IC50	1.6	nM	CHEMBL5744859
8.80	IC50	1.6	nM	CHEMBL5966636
8.80	IC50	1.6	nM	CHEMBL5897593
8.80	IC50	1.6	nM	CHEMBL6060186
8.77	Ki	1.698	nM	CHEMBL5267589
8.77	Ki	1.7	nM	CHEMBL5267589
8.74	IC50	1.8	nM	CHEMBL5825133
8.74	IC50	1.8	nM	CHEMBL6053091
8.74	IC50	1.8	nM	CHEMBL6001237
8.74	IC50	1.8	nM	CHEMBL5924278
8.74	IC50	1.8	nM	CHEMBL5741750
8.74	Ki	1.8	nM	CHEMBL1782887
8.72	IC50	1.9	nM	CHEMBL5765662
8.72	IC50	1.9	nM	CHEMBL5767114
8.70	IC50	2	nM	CHEMBL4101200
8.70	IC50	2	nM	CHEMBL5848269
8.68	IC50	2.1	nM	CHEMBL5837864
8.68	IC50	2.1	nM	CHEMBL5968090
8.66	IC50	2.2	nM	CHEMBL5791361
8.64	IC50	2.3	nM	CHEMBL5850219
8.64	IC50	2.3	nM	CHEMBL5901071
8.64	IC50	2.3	nM	CHEMBL5795417
8.62	IC50	2.4	nM	CHEMBL5848118
8.62	IC50	2.4	nM	CHEMBL5967006
8.62	IC50	2.4	nM	CHEMBL5903806
8.60	IC50	2.5	nM	CHEMBL5996078
8.59	IC50	2.6	nM	CHEMBL5813338
8.59	IC50	2.6	nM	CHEMBL5801079
8.59	IC50	2.6	nM	CHEMBL6063038
8.59	IC50	2.6	nM	CHEMBL6031498
8.57	IC50	2.7	nM	CHEMBL5756198
8.55	IC50	2.8	nM	CHEMBL5929981
8.54	IC50	2.9	nM	CHEMBL5841906
8.54	IC50	2.9	nM	CHEMBL5986707
8.54	IC50	2.9	nM	CHEMBL5757179
8.52	IC50	3	nM	CHEMBL5979812
8.52	IC50	3	nM	CHEMBL5950078
8.52	IC50	3	nM	CHEMBL5833643

PubChem BioAssay actives

206 with measured affinity, of 316 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
(2S)-2-[[(2S)-2-[(4S)-4-[[(2S,3S)-2-[[(2S)-2-[[(2R)-2-(aminomethyl)-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-oxo-1,4,5,10-tetrahydroazepino[3,4-b]indol-2-yl]pentanoyl]amino]-3-phenylpropanoic acid	1954036: Binding affinity to insulin regulated aminopeptidase (unknown origin)	ki	0.0017	uM
2-[2-[[[(2S,6S,9E,13S)-13-amino-2-[(4-hydroxyphenyl)methyl]-4,14-dioxo-1,5-diazacyclotetradec-9-ene-6-carbonyl]amino]methyl]phenyl]acetic acid	601497: Inhibition of catalytic activity of recombinant human IRAP transfected in human HEK-293 cells assessed as cleavage of substrate L-leucine-p-nitroanilide to L-leucine and p-nitroaniline measured every 5 mins for 10 to 50 mins by spectrophotometric analysis	ki	0.0018	uM
[(2S)-2-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]carbamoyl]pent-4-ynyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469764: Inhibition of IRAP (unknown origin) expressed in HEK 293S GnTI(-) cells by in vitro fluorimetric assay	ic50	0.0020	uM
2-[2-[[[(4R,8S,11S)-11-amino-8-[(4-hydroxyphenyl)methyl]-6,10-dioxo-1,2-dithia-5,9-diazacyclotridecane-4-carbonyl]amino]methyl]phenyl]acetic acid	537010: Inhibition of catalytic activity of human recombinant IRAP expressed in HEK293 cells	ki	0.0033	uM
[(2S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-2-[[3-(4-hydroxyphenyl)-1,2-oxazol-5-yl]methyl]-3-oxopropyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469764: Inhibition of IRAP (unknown origin) expressed in HEK 293S GnTI(-) cells by in vitro fluorimetric assay	ic50	0.0040	uM
2-[2-[[[(2S,5S,7E,13S)-13-amino-2-[(4-hydroxyphenyl)methyl]-3,14-dioxo-1,4-diazacyclotetradec-7-ene-5-carbonyl]amino]methyl]phenyl]acetic acid	601497: Inhibition of catalytic activity of recombinant human IRAP transfected in human HEK-293 cells assessed as cleavage of substrate L-leucine-p-nitroanilide to L-leucine and p-nitroaniline measured every 5 mins for 10 to 50 mins by spectrophotometric analysis	ki	0.0041	uM
2-[2-[[[(5S,9S,12S)-12-amino-9-[(4-hydroxyphenyl)methyl]-7,11-dioxo-1,2-dithia-6,10-diazacyclotetradecane-5-carbonyl]amino]methyl]phenyl]acetic acid	537010: Inhibition of catalytic activity of human recombinant IRAP expressed in HEK293 cells	ki	0.0052	uM
(2S)-2-[[(2S)-1-[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoic acid	344305: Displacement of [125I]Angiotensin 4 from human recombinant IRAP expressed in CHOK1 cells	ki	0.0070	uM
[(2S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-2-[[3-(2-hydroxyphenyl)-1,2-oxazol-5-yl]methyl]-3-oxopropyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469764: Inhibition of IRAP (unknown origin) expressed in HEK 293S GnTI(-) cells by in vitro fluorimetric assay	ic50	0.0090	uM
(2S)-2-[[(2S)-1-[(2S)-2-[[(2S,3S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoic acid	537008: Displacement of [3H]AL-11 from human IRAP expressed in CHO-K1 cells after 30 mins by liquid scintillation counting in presence of 30 mM EDTA/600 uM 1,10-Phe	ki	0.0093	uM
[(2S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-2-[[3-(4-methoxyphenyl)-1,2-oxazol-5-yl]methyl]-3-oxopropyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469764: Inhibition of IRAP (unknown origin) expressed in HEK 293S GnTI(-) cells by in vitro fluorimetric assay	ic50	0.0100	uM
[(2S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-2-[[3-(2-methoxyphenyl)-1,2-oxazol-5-yl]methyl]-3-oxopropyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469764: Inhibition of IRAP (unknown origin) expressed in HEK 293S GnTI(-) cells by in vitro fluorimetric assay	ic50	0.0130	uM
[(2S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-2-[[3-(2-chlorophenyl)-1,2-oxazol-5-yl]methyl]-3-oxopropyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469764: Inhibition of IRAP (unknown origin) expressed in HEK 293S GnTI(-) cells by in vitro fluorimetric assay	ic50	0.0130	uM
[(1R)-1-amino-3-phenylpropyl]-[(2S)-2-[(2S)-2-carbamoylpyrrolidine-1-carbonyl]-4-methylpentyl]phosphinic acid	1469764: Inhibition of IRAP (unknown origin) expressed in HEK 293S GnTI(-) cells by in vitro fluorimetric assay	ic50	0.0140	uM
[(2S)-2-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]carbamoyl]-4,4-diphenylbutyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469764: Inhibition of IRAP (unknown origin) expressed in HEK 293S GnTI(-) cells by in vitro fluorimetric assay	ic50	0.0160	uM
[(2S)-2-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]carbamoyl]-4,4-diphenylbutyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1443779: Inhibition of recombinant human IRAP expressed in GnT1 deficient HEK293S cells using L-leucine 7-amido-4-methyl coumarin as substrate after 5 to 10 mins by fluorimetric assay	ki	0.0180	uM
[(2S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-oxo-2-[(3-phenyl-1,2-oxazol-5-yl)methyl]propyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469764: Inhibition of IRAP (unknown origin) expressed in HEK 293S GnTI(-) cells by in vitro fluorimetric assay	ic50	0.0180	uM
(4R,8S,11S)-11-amino-N-benzyl-8-[(4-hydroxyphenyl)methyl]-6,10-dioxo-1,2-dithia-5,9-diazacyclotridecane-4-carboxamide	537010: Inhibition of catalytic activity of human recombinant IRAP expressed in HEK293 cells	ki	0.0185	uM
[(2S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-2-[[3-(3-methoxyphenyl)-1,2-oxazol-5-yl]methyl]-3-oxopropyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469764: Inhibition of IRAP (unknown origin) expressed in HEK 293S GnTI(-) cells by in vitro fluorimetric assay	ic50	0.0200	uM
ethyl 2-acetamido-7-hydroxy-4-quinolin-3-yl-4H-chromene-3-carboxylate	537010: Inhibition of catalytic activity of human recombinant IRAP expressed in HEK293 cells	ki	0.0200	uM
(3S)-3-[[(2S)-1-[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-4-phenylbutanoic acid	329317: Inhibition of human recombinant IRAP expressed in HEK293 cells	ki	0.0204	uM
[(2S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-2-[(3,5-diphenylphenyl)methyl]-3-oxopropyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469764: Inhibition of IRAP (unknown origin) expressed in HEK 293S GnTI(-) cells by in vitro fluorimetric assay	ic50	0.0210	uM
2-[2-[[[(5R,8S,11R)-11-amino-8-[(4-hydroxyphenyl)methyl]-7,10-dioxo-1,2-dithia-6,9-diazacyclotridecane-5-carbonyl]amino]methyl]phenyl]acetic acid	537010: Inhibition of catalytic activity of human recombinant IRAP expressed in HEK293 cells	ki	0.0225	uM
2-[2-[[[(2S,5S,13S)-13-amino-2-[(4-hydroxyphenyl)methyl]-3,14-dioxo-1,4-diazacyclotetradecane-5-carbonyl]amino]methyl]phenyl]acetic acid	601497: Inhibition of catalytic activity of recombinant human IRAP transfected in human HEK-293 cells assessed as cleavage of substrate L-leucine-p-nitroanilide to L-leucine and p-nitroaniline measured every 5 mins for 10 to 50 mins by spectrophotometric analysis	ki	0.0250	uM
(3S)-3-[[(2S)-1-[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2R)-2-(aminomethyl)-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-4-phenylbutanoic acid	1954036: Binding affinity to insulin regulated aminopeptidase (unknown origin)	ki	0.0275	uM
[(2S)-2-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamoyl]-4-methylpentyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469764: Inhibition of IRAP (unknown origin) expressed in HEK 293S GnTI(-) cells by in vitro fluorimetric assay	ic50	0.0290	uM
[(2S)-2-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamoyl]-4-methylpentyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1199908: Inhibition of human recombinant IRAP expressed in baculovirus infected cabbage looper ovary Hi5 cells using L-leucine-7-amido-4-methyl coumarin as substrate after 5 to 10 mins by fluorescence assay	ic50	0.0300	uM
2-[2-[[[(2S,6S,9S,12Z)-9-amino-6-[(4-hydroxyphenyl)methyl]-4,8-dioxo-1,3,7-triazacyclotetradec-12-ene-2-carbonyl]amino]methyl]phenyl]acetic acid	601497: Inhibition of catalytic activity of recombinant human IRAP transfected in human HEK-293 cells assessed as cleavage of substrate L-leucine-p-nitroanilide to L-leucine and p-nitroaniline measured every 5 mins for 10 to 50 mins by spectrophotometric analysis	ki	0.0304	uM
[(2S)-2-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]carbamoyl]-4-methylpentyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469764: Inhibition of IRAP (unknown origin) expressed in HEK 293S GnTI(-) cells by in vitro fluorimetric assay	ic50	0.0320	uM
[(2S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-2-[[3-(4-chlorophenyl)-1,2-oxazol-5-yl]methyl]-3-oxopropyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469764: Inhibition of IRAP (unknown origin) expressed in HEK 293S GnTI(-) cells by in vitro fluorimetric assay	ic50	0.0340	uM
2-[2-[[[(5R,9S,12S)-12-amino-9-[(4-hydroxyphenyl)methyl]-7,11-dioxo-1,2-dithia-6,10-diazacyclotetradecane-5-carbonyl]amino]methyl]phenyl]acetic acid	537008: Displacement of [3H]AL-11 from human IRAP expressed in CHO-K1 cells after 30 mins by liquid scintillation counting in presence of 30 mM EDTA/600 uM 1,10-Phe	ki	0.0349	uM
[(2S)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-2-[[3-(3-chlorophenyl)-1,2-oxazol-5-yl]methyl]-3-oxopropyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469764: Inhibition of IRAP (unknown origin) expressed in HEK 293S GnTI(-) cells by in vitro fluorimetric assay	ic50	0.0410	uM
[(2S)-2-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]carbamoyl]-4-methylpentyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469764: Inhibition of IRAP (unknown origin) expressed in HEK 293S GnTI(-) cells by in vitro fluorimetric assay	ic50	0.0410	uM
2-[2-[[[(2S,5S,8Z,12S)-12-amino-2-[(4-hydroxyphenyl)methyl]-3,13-dioxo-1,4-diazacyclotridec-8-ene-5-carbonyl]amino]methyl]phenyl]acetic acid	601497: Inhibition of catalytic activity of recombinant human IRAP transfected in human HEK-293 cells assessed as cleavage of substrate L-leucine-p-nitroanilide to L-leucine and p-nitroaniline measured every 5 mins for 10 to 50 mins by spectrophotometric analysis	ki	0.0411	uM
[(2S)-2-(1-adamantylmethyl)-3-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-oxopropyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469764: Inhibition of IRAP (unknown origin) expressed in HEK 293S GnTI(-) cells by in vitro fluorimetric assay	ic50	0.0460	uM
2-[2-[[[(2S,5S,8E,12S)-12-amino-2-[(4-hydroxyphenyl)methyl]-3,13-dioxo-1,4-diazacyclotridec-8-ene-5-carbonyl]amino]methyl]phenyl]acetic acid	601497: Inhibition of catalytic activity of recombinant human IRAP transfected in human HEK-293 cells assessed as cleavage of substrate L-leucine-p-nitroanilide to L-leucine and p-nitroaniline measured every 5 mins for 10 to 50 mins by spectrophotometric analysis	ki	0.0500	uM
2-[[2-[[(2R)-2-benzyl-4-(hydroxyamino)-4-oxobutanoyl]amino]-3-methylpentanoyl]amino]-3-methylbutanoic acid	101205: Inhibitory activity against Leucine aminopeptidase	ki	0.0520	uM
(5S,8S,11S)-11-amino-N-benzyl-8-[(4-hydroxyphenyl)methyl]-7,10-dioxo-1,2-dithia-6,9-diazacyclotridecane-5-carboxamide	537008: Displacement of [3H]AL-11 from human IRAP expressed in CHO-K1 cells after 30 mins by liquid scintillation counting in presence of 30 mM EDTA/600 uM 1,10-Phe	ki	0.0548	uM
2-[2-[[[(2S,5S,12S)-12-amino-2-[(4-hydroxyphenyl)methyl]-3,13-dioxo-1,4-diazacyclotridecane-5-carbonyl]amino]methyl]phenyl]acetic acid	601497: Inhibition of catalytic activity of recombinant human IRAP transfected in human HEK-293 cells assessed as cleavage of substrate L-leucine-p-nitroanilide to L-leucine and p-nitroaniline measured every 5 mins for 10 to 50 mins by spectrophotometric analysis	ki	0.0642	uM
(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-2-methyl-3-phenylbutanoic acid	1954036: Binding affinity to insulin regulated aminopeptidase (unknown origin)	ki	0.0759	uM
(2S)-2-[[2-[(7S)-7-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-6-oxo-7,8-dihydro-4H-triazolo[1,5-a][1,4]diazepin-5-yl]acetyl]amino]-3-phenylpropanoic acid	1954036: Binding affinity to insulin regulated aminopeptidase (unknown origin)	ki	0.0813	uM
(2S)-2-[[(2R)-1-[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]piperidine-2-carbonyl]amino]-3-phenylpropanoic acid	329317: Inhibition of human recombinant IRAP expressed in HEK293 cells	ki	0.0813	uM
(4R,8S,11S)-11-amino-8-[(4-hydroxyphenyl)methyl]-6,10-dioxo-N-(pyridin-3-ylmethyl)-1,2-dithia-5,9-diazacyclotridecane-4-carboxamide	537010: Inhibition of catalytic activity of human recombinant IRAP expressed in HEK293 cells	ki	0.0937	uM
(2S)-2-[[(2S)-1-[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2R)-2-(aminomethyl)-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoic acid	329317: Inhibition of human recombinant IRAP expressed in HEK293 cells	ki	0.1000	uM
[(2S)-2-[[(2S)-1-amino-1-oxopropan-2-yl]carbamoyl]-4-methylpentyl]-[(1R)-1-amino-3-phenylpropyl]phosphinic acid	1469764: Inhibition of IRAP (unknown origin) expressed in HEK 293S GnTI(-) cells by in vitro fluorimetric assay	ic50	0.1020	uM
benzyl (2S)-2-[[4-amino-3-[[(2S)-2-aminohexanoyl]amino]benzoyl]amino]-3-(1H-indol-3-yl)propanoate	1199908: Inhibition of human recombinant IRAP expressed in baculovirus infected cabbage looper ovary Hi5 cells using L-leucine-7-amido-4-methyl coumarin as substrate after 5 to 10 mins by fluorescence assay	ic50	0.1050	uM
(2S)-2-[[[(2S)-1-[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]methyl]-3-phenylpropanoic acid	329317: Inhibition of human recombinant IRAP expressed in HEK293 cells	ki	0.1096	uM
(2S)-2-[[2-[(2S)-1-[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidin-2-yl]acetyl]amino]-3-phenylpropanoic acid	329317: Inhibition of human recombinant IRAP expressed in HEK293 cells	ki	0.1445	uM
(2S)-2-[[(2S)-1-[(2S)-2-[[(3S,4S)-3-[[(2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylhexanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-phenylpropanoic acid	329317: Inhibition of human recombinant IRAP expressed in HEK293 cells	ki	0.1479	uM
(2S)-2-[[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-carboxy-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]methyl]-4-methylpentanoic acid	329317: Inhibition of human recombinant IRAP expressed in HEK293 cells	ki	0.1660	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment	4
bisphenol A	decreases expression, decreases methylation, increases expression	3
trichostatin A	increases expression, affects cotreatment	3
Aflatoxin B1	increases expression, affects expression, decreases methylation	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
Arsenic	affects cotreatment, decreases expression, increases abundance, affects methylation	2
Benzo(a)pyrene	increases expression, increases methylation	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
pyrogallol 1,3-dimethyl ether	increases expression, affects localization, affects cotreatment	1
2-butenal	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
pentabromodiphenyl ether	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment, increases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1

ChEMBL screening assays

34 unique, capped per target: 33 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1100890	Binding	Inhibition of catalytic activity of human IRAP transfected in HEK293 cells assessed as formation of p-nitroaniline	The replacement of His(4) in angiotensin IV by conformationally constrained residues provides highly potent and selective analogues. — J Med Chem
CHEMBL4334276	ADMET	Stability in pH 2 HCl assessed as aminopeptidase (unknown origin)-mediated compound hydrolysis by measuring parent compound remaining at 200 uM up to 6 hrs by RP-HPLC analysis	Astratides: Insulin-Modulating, Insecticidal, and Antifungal Cysteine-Rich Peptides from Astragalus membranaceus. — J Nat Prod

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.