PPIA

Summary

PPIA (peptidylprolyl isomerase A, HGNC:9253) is a protein-coding gene on chromosome 7p13, encoding Peptidyl-prolyl cis-trans isomerase A (P62937). Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. It is a selective cancer dependency (DepMap: 80.0% of cell lines).

This gene encodes a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. The encoded protein is a cyclosporin binding-protein and may play a role in cyclosporin A-mediated immunosuppression. The protein can also interact with several HIV proteins, including p55 gag, Vpr, and capsid protein, and has been shown to be necessary for the formation of infectious HIV virions. Multiple pseudogenes that map to different chromosomes have been reported.

Source: NCBI Gene 5478 — RefSeq curated summary.

At a glance

• Gene–disease (curated): amyotrophic lateral sclerosis (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 12 total
• GTEx eGene: eQTL in 35 tissues, sQTL in 17 (q < 0.05)
• Drug target: yes — 3 curated mechanism-of-action drugs; 6 molecules with ChEMBL bioactivity
• Approved drugs (ChEMBL mechanism of action): 1 — Cyclosporine
• Cancer dependency (DepMap): dependent in 80.0% of screened cell lines
• Constraint (gnomAD): pLI 0.98 (loss-of-function intolerant), LOEUF 0.43 (moderately constrained)
• MANE Select transcript: NM_021130

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9253
Approved symbol	PPIA
Name	peptidylprolyl isomerase A
Location	7p13
Locus type	gene with protein product
Status	Approved
Aliases	CYPA
Ensembl gene	ENSG00000196262
Ensembl biotype	protein_coding
OMIM	123840
Entrez	5478

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 28 protein_coding, 14 nonsense_mediated_decay, 5 retained_intron

MANE Select: ENST00000468812

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 5, TSL 3: 1, TSL 4: 1, TSL 5: 1

ENST00000468812, ENST00000355968, ENST00000415933, ENST00000451562, ENST00000479021, ENST00000480603, ENST00000481437, ENST00000489459, ENST00000494484, ENST00000620047, ENST00000676977, ENST00000677022, ENST00000677107, ENST00000677521, ENST00000678165, ENST00000678643, ENST00000678789, ENST00000678805, ENST00000891940, ENST00000915253, ENST00000915254, ENST00000915255, ENST00000915256, ENST00000915257, ENST00000915258, ENST00000915259, ENST00001056658, ENST00001056663, ENST00001079064, ENST00001079065, ENST00001079074, ENST00001079075, ENST00001079076, ENST00001104305, ENST00001104306, ENST00001104307, ENST00001104308, ENST00001104309, ENST00001104310, ENST00001104311, ENST00001104312, ENST00001104313, ENST00001104314, ENST00001104315, ENST00001104316, ENST00001104317, ENST00001139356

RefSeq mRNA: 2 — MANE Select: NM_021130 NM_001300981, NM_021130

CCDS: CCDS5494, CCDS75592

Canonical transcript exons

ENST00000468812 — 5 exons

Exon	Start	End
ENSE00001707052	44801287	44803117
ENSE00003486652	44796681	44796793
ENSE00003492091	44799702	44799874
ENSE00003540397	44799392	44799480
ENSE00003646478	44799247	44799277

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 99.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1218.1263 / max 24154.1773, expressed in 1829 samples.

Highest expression (Bgee): ventricular zone, frontal lobe, mucosa of transverse colon, anterior cingulate cortex, ganglionic eminence.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PPIA is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 35 tissues and its splicing (sQTL) in 17 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 52 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	1.7e-24	+0.20	7:44796715:A:G
Skin Sun Exposed Lower leg	sqtl	1.7e-20	+0.58	7:44796715:A:G
Adipose Subcutaneous	sqtl	7.8e-17	+0.47	7:44796715:A:G
Skin Not Sun Exposed Suprapubic	sqtl	2.3e-15	-0.59	7:44796715:A:G
Thyroid	eqtl	5.6e-15	+0.18	7:44782891:C:T
Esophagus Mucosa	eqtl	3.6e-14	+0.15	7:44796715:A:G
Nerve Tibial	eqtl	9.2e-13	+0.16	7:44796715:A:G
Esophagus Muscularis	eqtl	2.7e-12	+0.22	7:44801732:A:AT
Cells Cultured fibroblasts	eqtl	7.7e-12	-0.21	7:44769051:G:C
Muscle Skeletal	eqtl	1.2e-11	-0.25	7:44783004:C:T
Adipose Visceral Omentum	eqtl	1.4e-11	+0.17	7:44796715:A:G
Adipose Subcutaneous	eqtl	2.2e-11	+0.23	7:44800660:A:G
Lung	eqtl	3.1e-11	-0.17	7:44832667:C:G
Cells EBV-transformed lymphocytes	eqtl	9.8e-11	-0.20	7:44886571:G:C
Skin Not Sun Exposed Suprapubic	eqtl	5.8e-10	+0.17	7:44796715:A:G
Cells Cultured fibroblasts	sqtl	9.4e-09	+0.21	7:44796715:A:G
Breast Mammary Tissue	sqtl	8.0e-08	+0.45	7:44796715:A:G
Colon Transverse	sqtl	1.9e-07	-0.45	7:44886571:G:C
Pancreas	eqtl	4.8e-07	-0.33	7:44871083:G:T
Artery Tibial	eqtl	8.0e-07	+0.12	7:44796715:A:G

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
78443	1218.0820	1829
78444	0.0442	16

Top tissues by expression

showing 100 of 288 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.90	gold quality
right frontal lobe	UBERON:0002810	99.87	gold quality
mucosa of transverse colon	UBERON:0004991	99.86	gold quality
anterior cingulate cortex	UBERON:0009835	99.86	gold quality
ganglionic eminence	UBERON:0004023	99.84	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.84	gold quality
metanephros cortex	UBERON:0010533	99.83	gold quality
stromal cell of endometrium	CL:0002255	99.82	gold quality
rectum	UBERON:0001052	99.81	gold quality
cerebellar hemisphere	UBERON:0002245	99.81	gold quality
cortical plate	UBERON:0005343	99.81	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.80	gold quality
cerebellar cortex	UBERON:0002129	99.79	gold quality
upper lobe of left lung	UBERON:0008952	99.77	gold quality
right adrenal gland	UBERON:0001233	99.74	gold quality
right lung	UBERON:0002167	99.74	gold quality
adrenal tissue	UBERON:0018303	99.74	gold quality
granulocyte	CL:0000094	99.73	gold quality
right lobe of thyroid gland	UBERON:0001119	99.73	gold quality
left lobe of thyroid gland	UBERON:0001120	99.73	gold quality
skin of abdomen	UBERON:0001416	99.73	gold quality
left coronary artery	UBERON:0001626	99.73	gold quality
lower esophagus mucosa	UBERON:0035834	99.73	gold quality
left adrenal gland	UBERON:0001234	99.72	gold quality
skin of leg	UBERON:0001511	99.72	gold quality
right adrenal gland cortex	UBERON:0035827	99.72	gold quality
right coronary artery	UBERON:0001625	99.71	gold quality
adenohypophysis	UBERON:0002196	99.71	gold quality
transverse colon	UBERON:0001157	99.70	gold quality
ascending aorta	UBERON:0001496	99.70	gold quality
thoracic aorta	UBERON:0001515	99.70	gold quality
gall bladder	UBERON:0002110	99.70	gold quality
left adrenal gland cortex	UBERON:0035825	99.70	gold quality
monocyte	CL:0000576	99.69	gold quality
popliteal artery	UBERON:0002250	99.69	gold quality
descending thoracic aorta	UBERON:0002345	99.69	gold quality
tibial artery	UBERON:0007610	99.69	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.68	gold quality
ectocervix	UBERON:0012249	99.68	gold quality
lower esophagus	UBERON:0013473	99.68	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.68	gold quality
endocervix	UBERON:0000458	99.67	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.67	gold quality
small intestine Peyer’s patch	UBERON:0003454	99.66	gold quality
right testis	UBERON:0004534	99.66	gold quality
body of uterus	UBERON:0009853	99.66	gold quality
left uterine tube	UBERON:0001303	99.65	gold quality
minor salivary gland	UBERON:0001830	99.65	gold quality
cingulate cortex	UBERON:0003027	99.65	gold quality
muscle layer of sigmoid colon	UBERON:0035805	99.65	gold quality
right uterine tube	UBERON:0001302	99.64	gold quality
right ovary	UBERON:0002118	99.64	gold quality
left testis	UBERON:0004533	99.64	gold quality
body of stomach	UBERON:0001161	99.63	gold quality
left ovary	UBERON:0002119	99.63	gold quality
body of pancreas	UBERON:0001150	99.61	gold quality
tibial nerve	UBERON:0001323	99.61	gold quality
aorta	UBERON:0000947	99.60	gold quality
mucosa of stomach	UBERON:0001199	99.60	gold quality
omental fat pad	UBERON:0010414	99.54	gold quality
right lobe of liver	UBERON:0001114	99.53	gold quality
peritoneum	UBERON:0002358	99.52	gold quality
calcaneal tendon	UBERON:0003701	99.52	gold quality
right atrium auricular region	UBERON:0006631	99.43	gold quality
colonic epithelium	UBERON:0000397	99.41	gold quality
esophagus	UBERON:0001043	99.40	gold quality
apex of heart	UBERON:0002098	99.32	gold quality
leukocyte	CL:0000738	99.28	gold quality
mononuclear cell	CL:0000842	99.23	gold quality
esophagus mucosa	UBERON:0002469	99.22	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.22	gold quality
nucleus accumbens	UBERON:0001882	99.19	gold quality
vagina	UBERON:0000996	99.09	gold quality
caudate nucleus	UBERON:0001873	99.05	gold quality
upper lobe of lung	UBERON:0008948	99.03	gold quality
adipose tissue of abdominal region	UBERON:0007808	99.01	gold quality
prefrontal cortex	UBERON:0000451	98.99	gold quality
coronary artery	UBERON:0001621	98.99	gold quality
thyroid gland	UBERON:0002046	98.85	gold quality
amygdala	UBERON:0001876	98.75	gold quality
mouth mucosa	UBERON:0003729	98.72	gold quality
adrenal gland	UBERON:0002369	98.71	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.63	gold quality
stomach	UBERON:0000945	98.62	gold quality
adrenal cortex	UBERON:0001235	98.55	gold quality
tonsil	UBERON:0002372	98.26	gold quality
saliva-secreting gland	UBERON:0001044	98.19	gold quality
spinal cord	UBERON:0002240	98.19	gold quality
pituitary gland	UBERON:0000007	98.14	gold quality
gastrocnemius	UBERON:0001388	98.10	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.01	gold quality
spleen	UBERON:0002106	97.97	gold quality
testis	UBERON:0000473	97.96	gold quality
small intestine	UBERON:0002108	97.90	gold quality
cerebellum	UBERON:0002037	97.86	gold quality
ovary	UBERON:0000992	97.84	gold quality
muscle of leg	UBERON:0001383	97.67	gold quality
neocortex	UBERON:0001950	97.63	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.61	gold quality
pancreas	UBERON:0001264	97.58	gold quality

Single-cell (SCXA)

Detected in 26 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	50.12
E-CURD-112	yes	43.38
E-CURD-122	yes	28.88
E-MTAB-8410	yes	28.53
E-CURD-46	yes	26.56
E-HCAD-31	yes	19.48
E-MTAB-10042	yes	17.56
E-HCAD-1	yes	16.90
E-MTAB-7316	yes	11.38
E-CURD-88	yes	9.15
E-MTAB-10553	yes	9.04
E-CURD-79	no	3781.14
E-MTAB-10596	no	2864.62
E-MTAB-9435	no	2849.60
E-ENAD-21	no	2633.90

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 65 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thymus	tissue	2171.8
Tonsil	tissue	1539.2	medium
Breast	tissue	1278.9	medium
Colon	tissue	1264.0	medium
Urinary bladder	tissue	1247.8	medium
Vagina	tissue	1212.1	medium
Parathyroid gland	tissue	1206.1	not detected
Liver	tissue	1177.8	not detected
Rectum	tissue	1119.4	medium
Lymph node	tissue	994.7	medium
Bone marrow	tissue	992.0	medium
Ovary	tissue	990.7	not detected
Pons	tissue	983.1
Cerebral cortex	tissue	954.1	medium
Postcentral gyrus	tissue	954.1
Esophagus	tissue	928.9	medium
Epididymis	tissue	926.2	low
Kidney	tissue	921.1	medium
Smooth muscle	tissue	879.3	not detected
Medulla oblongata	tissue	873.3
Hypothalamus	tissue	846.7
Locus coeruleus	tissue	802.9
Cervix	tissue	799.4	medium
Spinal cord	tissue	789.1
Adipose tissue	tissue	782.6	not detected
Spleen	tissue	771.8	medium
Lung	tissue	767.3	medium
Placenta	tissue	755.6	medium
Basal ganglia	tissue	753.0	medium
Seminal vesicle	tissue	736.5	medium
Thalamus	tissue	733.1
Cerebellum	tissue	721.7	not detected
Skin 1	tissue	721.2	medium
Choroid plexus	tissue	692.8
Retrosplenial cortex	tissue	687.8
Stomach 1	tissue	673.0	medium
Hippocampal formation	tissue	672.5
Appendix	tissue	671.9	medium
Pituitary gland	tissue	660.0
Thyroid gland	tissue	649.4	medium
Midbrain	tissue	644.3
Occipital cortex	tissue	623.0
Amygdala	tissue	616.2
Substantia nigra	tissue	605.9
Nucleus accumbens	tissue	592.3
Hippocampus	tissue	590.8	low
Fallopian tube	tissue	575.9	medium
Salivary gland	tissue	572.0	medium
Small intestine	tissue	565.9	medium
Duodenum	tissue	565.8	low
Putamen	tissue	564.3
Prostate	tissue	559.3	medium
Adrenal gland	tissue	519.1	medium
Gallbladder	tissue	513.9	medium
Endometrium 1	tissue	496.9	medium
Pancreas	tissue	482.7	medium
Tongue	tissue	482.3
Retina	tissue	460.2
Heart muscle	tissue	439.4	not detected
Testis	tissue	254.4	medium

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Blood vessel (1240.6), Pontine nuclei (983.1), Nucleus raphe magnus (972.7), Nuclei of the trapezoid body (913.9), Lateral funiculus (white matter) (910.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CUX1, E2F4, HIF1A, KMT2A, TP53, TP73

miRNA regulators (miRDB)

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

showing 30 of 69 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-135A-5P	99.36	71.85	1601

Functional genomics

gnomAD constraint: pLI 0.985, LOEUF 0.429, missense Z 2.5 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000468812 — one region, missense o/e 0.49. DepMap (CRISPR cell-line fitness): dependent in 80.0% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): RD-ES (-1.432), MHH-NB-11 (-1.41), U-87 MG (-1.38), NCI-H460 (-1.353), SNU-5 (-1.344), SNU-685 (-1.328), IMR-32 (-1.307), JHH-4 (-1.298), Du4475 (-1.288), EFM-19 (-1.277), G-402 (-1.274), NCI-H520 (-1.259), IGR-39 (-1.254), CADO-ES1 (-1.225), NCI-H2122 (-1.224).

Literature-anchored findings (GeneRIF, showing 40)

• novel mode of tyrosine kinase regulation for a Tec family member and provide a molecular basis for understanding a cellular function of the ubiquitous peptidyl prolyl isomerase, CypA (PMID:11830645)
• NMR relaxation methods used to characterize conformational exchange during catalysis (PMID:11859194)
• Catalysis of cis/trans isomerization in native HIV-1 capsid by human cyclophilin A. (PMID:11929983)
• Active site residues of cyclophilin A are crucial for its signaling activity via CD147 (PMID:11943775)
• Effects of gag mutations on human immunodeficiency virus type 1 particle assembly, processing, and cyclophilin A incorporation. (PMID:12210402)
• Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes. (PMID:12218175)
• functional CypA required for Vesicular Stomatis Virus-New Jersey replication and infection; interacts with the nucleocapsid (N) protein of VSV-NJ and VSV-IND in infected cells, but not obligatory for the latter serotype. (PMID:12810862)
• Comparative molecular modeling of allergenic cyclophilin proteins, including cyclophilin A, was performed in order to investigate the structural basis of their cross-reactivity. (PMID:12859974)
• Cyclophilin A interacts with HIV-1 Vpr and is required for its functional expression (PMID:12881522)
• alternative splicing and role implicated in interaction with HIV-1 (PMID:14526201)
• CYPA and AIF cooperate in apoptosis-associated chromatinolysis. (PMID:14716299)
• CyPA is a novel paracrine and autocrine modulator of EC functions in immune-mediated vascular disease (PMID:15111303)
• Recombinant CyPA activated MAP kinases in cultured human umbilical vein EC & stimulated IkappaB-alpha phosphorylation, NF-kappaB activation, & adhesion molecule expression. It may play a role in the pathogenesis of inflammatory diseases. (PMID:15130913)
• Results suggest that the N-terminal domain of the capsid domain of the HIV-1 Gag precursor polyprotein is the preferential site for cyclophilin A binding. (PMID:15147195)
• Interaction energy and dynamical cross-correlation calculations are used for a detailed investigation of the protein-protein interactions in the cyclophilin A-HIV-1 capsid protein complex. (PMID:15229879)
• identify a network of protein vibrations, extending from surface regions of the enzyme to the active site and coupled to substrate turnover. Crucial parts of this network are found to be conserved in 10 cyclophilin structures from six different species. (PMID:15311922)
• Results describe the binding of severe acute respiratory syndrome coronavirus to human cyclophilin A. (PMID:15358143)
• cyclophilin A binds CD99 and may be either a signaling mediator or a signaling regulator for CD99 (PMID:15388255)
• affects the fate of incoming HIV-1 capsid either directly or by modulating interactions with unidentified host cell factors. (PMID:15596813)
• CypA substantially alters the mRNA levels of several key genes in human vascular cells, indicating potential multifunctional roles of CypA in vascular system. (PMID:15680395)
• x-ray crystallographic analysis of human cyclophilin A in complex with the novel immunosuppressant sanglifehrin A (PMID:15772070)
• The peptide FGPDLPAGD showed inhibition of the isomerase reaction and NMR chemical shift mapping experiments highlight the cyclophilin A interaction epitope (PMID:15845542)
• analysis of HIV-1 Gag protein interactions with cyclophilin A (PMID:16275650)
• protects HIV-1 from an unknown antiviral activity in human cells, completely independnet of TRIM5alpha (PMID:16501094)
• results support that Pseudomonas aeruginosa exoenzyme S ADP-ribosylates and affects the function of the cytosolic protein, CpA, with the predominant functional effect relating to interference of CpA-cellular protein interactions (PMID:16584201)
• PPIA, the c-myc-regulated gene is involved in genotype-C-HBV-related HCC, suggesting that c-myc is related to the hepatocarcinogenic activity of genotype-C HBV. (PMID:16703398)
• cyclophilin A and G2 cell cycle arrest appear to be two independent factors important for efficient lentiviral gene transfer (PMID:16901758)
• Diverse lentiviruses, FIV and SIVagmTAN also bind to CypA. (PMID:17038183)
• Results describe a novel vif-sensitive antiviral activity of human cyclophilin A that may limit zoonotic transmission of SIV and the first demonstration of CypA encapsidation into a virus other than human immunodeficiency virus type 1. (PMID:17522232)
• the expression of CypA and its receptor CD147 in several kinds of lung cancer cells as well as a normal lung cell and found that in H446 cell, a kind of small cell lung cancer cell, the expression are the highest (PMID:17678621)
• virus assembly and disassembly are attractive candidate processes for antiviral intervention; HIV-1 capsid (CA) protein and human cyclophilin A (CypA) play important roles in these processes (PMID:17897064)
• CyPA acts as a potent monocyte chemoattractant and induces monocyte Il-6 release, implying a role for extracellular CyPA in the pathogenesis of atherosclerosis via activation of monocytes rather than endothelial cells (PMID:17919644)
• most potent derivative binds CypA with a K(d) of 11.2+/-9.2 microM and an IC50 for activity against Caenorhabditis elegans (C. elegans) of 190 microM compared to 28 microM for cyclophilin A (PMID:17927958)
• Data show that cyclophilin A is required for CXCR4-mediated nuclear export of heterogeneous nuclear ribonucleoprotein A2,activation and nuclear translocation of ERK1/2, and chemotactic cell migration. (PMID:17991743)
• PPIA variation did not significantly contribute to the risk of suffering from myocardial infarction among patients with atherosclerotic diseased vessels. (PMID:18321308)
• reveal the molecular mechanism of cyclosporine resistance and identify CyPA as a critical cellular cofactor for HCV replication and infection (PMID:18385230)
• cyclophilin A gene was identified as the most suitable normaliser in gene expression studies involving human airway epithelial cells derived from normal, atopic and asthmatic children (PMID:18417509)
• These data suggest that cyclophilin A may serve as a novel prognostic factor and possibly an attractive therapeutic target for endometrial carcinoma. (PMID:18421009)
• cyclophilin-A promoter polymorphism (-11 G/C) could be associated with clinical nephrotoxicity. (PMID:18673375)
• Data suggest that cyclophilin A is required for stabilizing N-WASP to form a N-WASP/Arp2/3 complex for the nucleation/initiation of F-actin polymerization. (PMID:18704644)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppifa	ENSDARG00000007409
danio_rerio	ppiaa	ENSDARG00000009212
danio_rerio	ppiab	ENSDARG00000103994
drosophila_melanogaster	Cyp40	FBGN0036020
drosophila_melanogaster	Moca-cyp	FBGN0039581
caenorhabditis_elegans		WBGENE00000877
caenorhabditis_elegans		WBGENE00000878
caenorhabditis_elegans		WBGENE00000879
caenorhabditis_elegans		WBGENE00000883
caenorhabditis_elegans		WBGENE00000885

Paralogs (22): PPIE (ENSG00000084072), PPIL2 (ENSG00000100023), PPIF (ENSG00000108179), PPWD1 (ENSG00000113593), NKTR (ENSG00000114857), PPIL4 (ENSG00000131013), PPIL1 (ENSG00000137168), PPIG (ENSG00000138398), CWC27 (ENSG00000153015), PPIB (ENSG00000166794), PPIC (ENSG00000168938), PPID (ENSG00000171497), PPIH (ENSG00000171960), PPIL6 (ENSG00000185250), PPIAL4G (ENSG00000236334), PPIL3 (ENSG00000240344), PPIAL4A (ENSG00000263353), PPIAL4H (ENSG00000270339), PPIAL4E (ENSG00000271567), PPIAL4F (ENSG00000279782), PPIAL4C (ENSG00000288867), PPIAL4D (ENSG00000289549)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97749) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 39 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal snout morphology	1
abnormal colon morphology	1
abnormal spleen morphology	1
enlarged spleen	1
spleen hyperplasia	1
decreased body length	1
persistence of hyaloid vascular system	1
microphthalmia	1
cataract	1
increased inflammatory response	1
heart inflammation	1
liver inflammation	1
pancreas inflammation	1
abnormal eye morphology	1
abnormal kidney morphology	1
increased immunoglobulin level	1
increased IgE level	1
increased mean platelet volume	1
abnormal vitreous body morphology	1
megacolon	1
decreased heart weight	1
decreased erythrocyte cell number	1
increased circulating alkaline phosphatase level	1
small kidney	1
abnormal auditory brainstem response	1

+14 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
Trichophyton benhamiae CBS 112371	D4AY02	100.0%	Diamond
Trichophyton benhamiae	O93826	100.0%	Diamond
Cryptococcus deneoformans JEC21	P0CP78	100.0%	Diamond
Cryptococcus deneoformans B-3501A	P0CP79	100.0%	Diamond
Bos taurus	P62935	100.0%	Diamond
Sus scrofa	P62936	100.0%	Diamond
Chlorocebus aethiops	P62938	100.0%	Diamond
Macaca mulatta	P62940	100.0%	Diamond
Papio anubis	P62941	100.0%	Diamond
Saguinus oedipus	Q0ZQK3	100.0%	Diamond
Symphalangus syndactylus	Q0ZQK6	100.0%	Diamond
Nomascus leucogenys	Q0ZQK7	100.0%	Diamond
Hylobates lar	Q0ZQK8	100.0%	Diamond
Gorilla gorilla gorilla	Q0ZQL0	100.0%	Diamond
Pan troglodytes	Q0ZQL1	100.0%	Diamond
Pan paniscus	Q0ZQL2	100.0%	Diamond
Pongo pygmaeus	Q5R8S7	100.0%	Diamond
Aotus trivirgatus	Q6DTV9	100.0%	Diamond
Mus musculus	Q9D868	100.0%	Diamond
Pongo abelii	Q5R723	99.3%	Diamond
Cricetulus griseus	P14851	98.8%	Diamond
Rattus norvegicus	P29117	98.5%	Diamond
Felis catus	Q8HXS3	98.2%	Diamond
Schistosoma japonicum	Q26516	96.6%	Diamond
Schistosoma mansoni	Q26548	96.6%	Diamond
Oryctolagus cuniculus	Q9TTC6	96.3%	Diamond
Aspergillus oryzae RIB40	Q2U6U0	93.8%	Diamond
Aspergillus nidulans FGSC A4	Q5ASQ0	93.8%	Diamond
Aspergillus fumigatus Af293	Q4WCR3	93.2%	Diamond
Aspergillus niger	Q8X191	93.0%	Diamond
Glycine max	Q8W171	92.4%	Diamond
Arabidopsis thaliana	P34790	91.7%	Diamond
Catharanthus roseus	Q39613	91.3%	Diamond
Brassica napus	P24525	91.1%	Diamond
Fusarium graminearum PH-1	Q4IPH4	89.6%	Diamond
Neurospora crassa OR74A	Q7SG06	89.6%	Diamond
Gallus gallus	P24367	88.7%	Diamond
Lupinus luteus	O49886	88.4%	Diamond
Solanum lycopersicum	P21568	87.1%	Diamond
Neospora caninum	P84343	86.5%	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
ZMIZ2	protein-coding	83637
H2AZ2	protein-coding	94239
MIR4657	ncRNA	100616393
PURB	protein-coding	5814
OGDH	protein-coding	4967
H2AZ2-DT	ncRNA	105375261

Protein

Protein identifiers

Peptidyl-prolyl cis-trans isomerase A — P62937 (reviewed: P62937)

Alternative names: Cyclophilin A, Cyclosporin A-binding protein, Rotamase A

All UniProt accessions (8): A0A7I2V4V1, A0A7I2V5J5, A0A7P0S768, C9J5S7, E5RIZ5, P62937, F8WE65, V9HWF5

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Exerts a strong chemotactic effect on leukocytes partly through activation of one of its membrane receptors BSG/CD147, initiating a signaling cascade that culminates in MAPK/ERK activation. Activates endothelial cells (ECs) in a pro-inflammatory manner by stimulating activation of NF-kappa-B and ERK, JNK and p38 MAP-kinases and by inducing expression of adhesion molecules including SELE and VCAM1. Induces apoptosis in ECs by promoting the FOXO1-dependent expression of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis. In response to oxidative stress, initiates proapoptotic and antiapoptotic signaling in ECs via activation of NF-kappa-B and AKT1 and up-regulation of antiapoptotic protein BCL2. Negatively regulates MAP3K5/ASK1 kinase activity, autophosphorylation and oxidative stress-induced apoptosis mediated by MAP3K5/ASK1. Necessary for the assembly of TARDBP in heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and regulates TARDBP binding to RNA UG repeats and TARDBP-dependent expression of HDAC6, ATG7 and VCP which are involved in clearance of protein aggregates. Plays an important role in platelet activation and aggregation. Regulates calcium mobilization and integrin ITGA2B:ITGB3 bidirectional signaling via increased ROS production as well as by facilitating the interaction between integrin and the cell cytoskeleton. Binds heparan sulfate glycosaminoglycans. Inhibits replication of influenza A virus (IAV). Inhibits ITCH/AIP4-mediated ubiquitination of matrix protein 1 (M1) of IAV by impairing the interaction of ITCH/AIP4 with M1, followed by the suppression of the nuclear export of M1, and finally reduction of the replication of IAV. (Microbial infection) May act as a mediator between human SARS coronavirus nucleoprotein and BSG/CD147 in the process of invasion of host cells by the virus. (Microbial infection) Stimulates RNA-binding ability of HCV NS5A in a peptidyl-prolyl cis-trans isomerase activity-dependent manner. (Microbial infection) May act as a receptor for M.genitalium adhesin protein P140 (also called MgPa).

Subunit / interactions. Interacts with protein phosphatase PPP3CA/calcineurin A. Interacts with PRPF19 isoform 2 (via N-terminus). Interacts with isoform 2 of BSG/CD147. Interacts with FOXO1; the interaction promotes FOXO1 dephosphorylation, nuclear accumulation and transcriptional activity. Interacts with integrin ITGA2B:ITGB3; the interaction is ROS and peptidyl-prolyl cis-trans isomerase (PPIase) activity-dependent and is increased in the presence of thrombin. Interacts with MAP3K5. Interacts with TARDBP; the interaction is dependent on the RNA-binding activity of TARDBP and the PPIase activity of PPIA/CYPA and the acetylation of PPIA/CYPA at Lys-125 favors the interaction. Interacts with HNRNPA1, HNRNPA2B1, HNRNPC, RBMX, HNRNPK and HNRNPM. (Microbial infection) Interacts with HIV-1 capsid protein. (Microbial infection) Interacts with human SARS coronavirus nucleoprotein. (Microbial infection) Interacts with measles virus nucleoprotein. (Microbial infection) Interacts with influenza A virus matrix protein 1. (Microbial infection) Interacts with M.genitalium adhesin P140 protein (also called MgPa). (Microbial infection) Interacts with HCV NS5A; the interaction stimulates RNA-binding ability of NS5A and is dependent on the peptidyl-prolyl cis-trans isomerase activity of PPIA/CYPA.

Subcellular location. Cytoplasm. Secreted. Nucleus. Cell membrane Secreted.

Post-translational modifications. Acetylation at Lys-125 markedly inhibits catalysis of cis to trans isomerization and stabilizes cis rather than trans forms of the HIV-1 capsid. PPIA acetylation also antagonizes the immunosuppressive effects of cyclosporine by inhibiting the sequential steps of cyclosporine binding and calcineurin inhibition (PubMed:20364129, Ref.12). Acetylation at Lys-125 favors its interaction with TARDBP.

Activity regulation. Binds cyclosporin A (CsA). CsA mediates some of its effects via an inhibitory action on PPIase.

Similarity. Belongs to the cyclophilin-type PPIase family. PPIase A subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P62937-1	1	yes
P62937-2	2

RefSeq proteins (2): NP_001287910, NP_066953* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002130	Cyclophilin-type_PPIase_dom	Domain
IPR020892	Cyclophilin-type_PPIase_CS	Conserved_site
IPR024936	Cyclophilin-type_PPIase	Family
IPR029000	Cyclophilin-like_dom_sf	Homologous_superfamily

Pfam: PF00160

Enzyme classification (BRENDA)

• EC 5.2.1.8 — peptidylprolyl isomerase (BRENDA: 69 organisms, 374 substrates, 222 inhibitors, 24 Km, 30 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
N-SUCCINYL-ALA-GLU-(TRANS)-PRO-PHE-4-NITROANILID	0.17–0.7	5
N-SUCCINYL-ALA-ALA-(CIS)-PRO-PHE-4-NITROANILIDE	0.104–0.814	2
RNASE T1	0.0004–0.0006	2
SUCCINYL-ALA-ALA-PRO-PHE 4-NITROANILIDE	0.451–1.247	2
SUCCINYL-ALA-LYS-PRO-PHE-4-NITROANILIDE	0.585–0.788	2
ALA-GLY-PSI[CS-N]-PRO-PHE-4-NITROANILIDE	0.53	1
N-SUCCINYL-ALA-LEU-(CIS)-PRO-PHE-4-NITROANILIDE	0.059	1
SUCCINYL-ALA-GLU-PRO-PHE-7-AMIDO-4-METHYLCOUMARI	0.12	1
TRYWNAKMK-(CIS)-PFIFGA	2	1
SUCCINYL-ALA-ALA-(CIS)-PRO-LYS-4-METHYLCOUMARIN-	—	0
SUCCINYL-ALA-ALA-(CIS)-PRO-PHE 4-METHYLCOUMARIN	—	0

Catalyzed reactions (Rhea)

• [protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0) (RHEA:16237)

UniProt features (59 total): strand 15, mutagenesis site 13, modified residue 11, helix 4, turn 4, cross-link 3, sequence conflict 3, chain 2, initiator methionine 1, glycosylation site 1, splice variant 1, domain 1

Structure

Experimental structures (PDB)

showing 30 of 205 structures by resolution:

PDB	Title	Method	Resolution (Å)
9E3S	Tricomplex of RMC-9945, KRAS G12N, and CypA	X-RAY DIFFRACTION	1.08
9BG4	Tri-complex of Compound-2, KRAS G12V, and CypA	X-RAY DIFFRACTION	1.14
4N1M	Structure of Cyclophilin A in complex with GlyPro.	X-RAY DIFFRACTION	1.15
5F66	High-resolution isotropic multiconformer synchrotron model of CypA at 273 K	X-RAY DIFFRACTION	1.15
9GHY	Cyclophilin A in complex with Sanglifehrin A analogue …	X-RAY DIFFRACTION	1.15
6GJL	Cyclophilin A complexed with tri-vector ligand 10.	X-RAY DIFFRACTION	1.16
6GS6	Cyclophilin A single mutant D66A in complex with an inhibitor.	X-RAY DIFFRACTION	1.16
2X25	Free acetyl-CypA orthorhombic form	X-RAY DIFFRACTION	1.2
4YUO	High-resolution multiconformer synchrotron model of CypA at 273 K	X-RAY DIFFRACTION	1.2
7UXM	Structure of PPIA in complex with FP29092, a Helicon Polypeptide	X-RAY DIFFRACTION	1.2
8TBG	Tricomplex of RMC-7977, HRAS WT, and CypA	X-RAY DIFFRACTION	1.2
9BFV	Tri-complex of Compound-23, KRAS G12C, and CypA	X-RAY DIFFRACTION	1.2
9BFW	Tri-complex of Compound-4, KRAS G12C, and CypA	X-RAY DIFFRACTION	1.2
9BG8	Tri-complex of Daraxonrasib (RMC-6236), NRAS Q61R, and CypA	X-RAY DIFFRACTION	1.2
36OK	Tri-complex of RMC-8839, KRAS G13C, and CypA	X-RAY DIFFRACTION	1.21
3K0M	Cryogenic structure of CypA	X-RAY DIFFRACTION	1.25
5LUD	Structure of Cyclophilin A in complex with 2,3-Diaminopyridine	X-RAY DIFFRACTION	1.25
8TBK	Tricomplex of RMC-7977, KRAS G12C, and CypA	X-RAY DIFFRACTION	1.26
9BFY	Tri-complex of Compound-14, KRAS G12C, and CypA	X-RAY DIFFRACTION	1.26
9CT8	Tricomplex of Compound 2, KRAS G12D, and CypA	X-RAY DIFFRACTION	1.28
6GJY	Cyclophilin A complexed with tri-vector ligand 5.	X-RAY DIFFRACTION	1.29
9CTA	Tricomplex of RMC-9945, KRAS G12D, and CypA	X-RAY DIFFRACTION	1.29
9CTB	Tri-complex of zoldonrasib (RMC-9805), KRAS G12D, and CypA	X-RAY DIFFRACTION	1.29
5NOU	Structure of cyclophilin A in complex with hexahydropyrimidin-2-one	X-RAY DIFFRACTION	1.3
7ABT	Structure of PPIA in complex with PR dipeptide repeat	X-RAY DIFFRACTION	1.31
9BG3	Tri-complex of Daraxonrasib (RMC-6236), NRAS Q61K, and CypA	X-RAY DIFFRACTION	1.33
4YUH	Multiconformer synchrotron model of CypA at 150 K	X-RAY DIFFRACTION	1.34
5NOS	Structure of cyclophilin A in complex with 3-amino-1H-pyridin-2-one	X-RAY DIFFRACTION	1.35
9CT9	Tricomplex of Compound 3, KRAS G12D, and CypA	X-RAY DIFFRACTION	1.35
6GJM	Cyclophilin A complexed with tri-vector ligand 4.	X-RAY DIFFRACTION	1.35

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62937-F1	98.05	0.99

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Isomerase, Metabolic proteins, Predicted secreted proteins, Predicted intracellular proteins, Plasma proteins, FDA approved drug targets, Small molecule drugs, Essential proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH uncertain

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 (14)

Type	Positions
N6-acetyllysine	82, 125, 131, 133, 28, 44, 76
Phosphothreonine	93
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	28, 82
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in ubiquitin)	28
N-acetylmethionine	1
N-acetylvaline	2
Phosphoserine	77

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	108

Mutagenesis-validated functional residues (13)

Position	Phenotype
55	loss of peptidyl-prolyl cis-trans isomerase activity. no loss of its interaction with bsg/cd147 or its ability to induce leukocyte …
60	loss of ability to stimulate mapk/erk phosphorylation.
69	no effect on peptidyl-prolyl cis-trans isomerase activity. reduced interaction with bsg/cd147 and ability to induce leukocyte chemotaxis.
70	no effect on peptidyl-prolyl cis-trans isomerase activity. reduced interaction with bsg/cd147 and ability to induce leukocyte chemotaxis.
107	no effect on peptidyl-prolyl cis-trans isomerase activity. reduced interaction with bsg/cd147 and ability to induce leukocyte chemotaxis.
113	reduced ability to stimulate mapk/erk phosphorylation.
121	200-fold decrease of sensitivity to csa. reduced ability to stimulate mapk/erk phosphorylation.
121	loss of peptidyl-prolyl cis-trans isomerase activity.
121	75-fold decrease of sensitivity to csa.
121	no effect on peptidyl-prolyl cis-trans isomerase activity.
125	acetylation-mimetic mutant; no effect on its interaction with tardbp.
125	loss of acetylation and interaction with tardbp.
126	loss of peptidyl-prolyl cis-trans isomerase activity and interaction with hcv ns5a. loss of ability to stimulate mapk/erk phosphorylation.

Function

Pathways and Gene Ontology

Reactome pathways

13 curated (TAS) of 39; 21 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

39 pathways:

ID	Pathway	Evidence
R-HSA-180689	APOBEC3G mediated resistance to HIV-1 infection ⚕	curated
R-HSA-175474	Assembly Of The HIV Virion ⚕	curated
R-HSA-173107	Binding and entry of HIV virion ⚕	curated
R-HSA-162588	Budding and maturation of HIV virion ⚕	curated
R-HSA-162594	Early Phase of HIV Life Cycle ⚕	curated
R-HSA-162592	Integration of provirus ⚕	curated
R-HSA-164516	Minus-strand DNA synthesis ⚕	curated
R-HSA-164525	Plus-strand DNA synthesis ⚕	curated
R-HSA-9692916	SARS-CoV-1 activates/modulates innate immune responses ⚕	curated
R-HSA-162585	Uncoating of the HIV Virion ⚕	curated
R-HSA-210991	Basigin interactions	curated
R-HSA-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	curated
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-162906	HIV Infection ⚕	—
R-HSA-162587	HIV Life Cycle ⚕	—
R-HSA-162909	Host Interactions of HIV factors ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-162599	Late Phase of HIV Life Cycle ⚕	—
R-HSA-162589	Reverse Transcription of HIV RNA ⚕	—
R-HSA-9679506	SARS-CoV Infections ⚕	—
R-HSA-9678108	SARS-CoV-1 Infection ⚕	—
R-HSA-9692914	SARS-CoV-1-host interactions ⚕	—
R-HSA-9824446	Viral Infection Pathways ⚕	—
R-HSA-1280218	Adaptive Immune System	—
R-HSA-2025928	Calcineurin activates NFAT	electronic
R-HSA-202733	Cell surface interactions at the vascular wall	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-1168372	Downstream signaling events of B Cell Receptor (BCR)	—
R-HSA-109582	Hemostasis	—
R-HSA-168256	Immune System	—
R-HSA-168249	Innate Immune System	—
R-HSA-447115	Interleukin-12 family signaling	—
R-HSA-9020591	Interleukin-12 signaling	—
R-HSA-76002	Platelet activation, signaling and aggregation	—
R-HSA-114608	Platelet degranulation	electronic
R-HSA-76005	Response to elevated platelet cytosolic Ca2+	—
R-HSA-449147	Signaling by Interleukins	—
R-HSA-983705	Signaling by the B Cell Receptor (BCR)	—

MSigDB gene sets: 412 (showing top): HORIUCHI_WTAP_TARGETS_DN, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_MYELOID_LEUKOCYTE_MIGRATION, REACTOME_INTEGRATION_OF_PROVIRUS, GOBP_CELL_CHEMOTAXIS, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_PLATELET_ACTIVATION, GCM_NPM1, MORF_UBE2I

GO Biological Process (25): protein peptidyl-prolyl isomerization (GO:0000413), negative regulation of protein phosphorylation (GO:0001933), positive regulation of protein phosphorylation (GO:0001934), protein folding (GO:0006457), negative regulation of protein kinase activity (GO:0006469), apoptotic process (GO:0006915), viral release from host cell (GO:0019076), platelet activation (GO:0030168), neutrophil chemotaxis (GO:0030593), leukocyte chemotaxis (GO:0030595), activation of protein kinase B activity (GO:0032148), negative regulation of stress-activated MAPK cascade (GO:0032873), lipid droplet organization (GO:0034389), cellular response to oxidative stress (GO:0034599), endothelial cell activation (GO:0042118), positive regulation of MAPK cascade (GO:0043410), regulation of viral genome replication (GO:0045069), positive regulation of viral genome replication (GO:0045070), positive regulation of protein secretion (GO:0050714), cell adhesion molecule production (GO:0060352), negative regulation of protein K48-linked ubiquitination (GO:0061944), platelet aggregation (GO:0070527), negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway (GO:1902176), negative regulation of viral life cycle (GO:1903901), regulation of apoptotic signaling pathway (GO:2001233)

GO Molecular Function (8): RNA binding (GO:0003723), peptidyl-prolyl cis-trans isomerase activity (GO:0003755), integrin binding (GO:0005178), cyclosporin A binding (GO:0016018), virion binding (GO:0046790), heparan sulfate binding (GO:1904399), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (12): extracellular region (GO:0005576), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), membrane (GO:0016020), vesicle (GO:0031982), protein-containing complex (GO:0032991), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062), ficolin-1-rich granule lumen (GO:1904813)

Reactome top-level categories

14 top-level categories:

Category	Pathways
Early Phase of HIV Life Cycle	3
Late Phase of HIV Life Cycle	2
Reverse Transcription of HIV RNA	2
Immune System	2
Response to elevated platelet cytosolic Ca2+	1
HIV Life Cycle	1
Host Interactions of HIV factors	1
Downstream signaling events of B Cell Receptor (BCR)	1
Cell surface interactions at the vascular wall	1
Innate Immune System	1
Interleukin-12 signaling	1
SARS-CoV-1-host interactions	1
Signaling by the B Cell Receptor (BCR)	1
HIV Infection	1

GO top-level categories

showing 60 of 70 GO namespaces:

Category	Terms
cellular anatomical structure	4
regulation of protein phosphorylation	2
protein phosphorylation	2
cellular process	2
cell activation	2
viral genome replication	2
binding	2
peptidyl-proline modification	1
negative regulation of protein modification process	1
negative regulation of phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
protein maturation	1
negative regulation of protein phosphorylation	1
protein kinase activity	1
negative regulation of kinase activity	1
regulation of protein kinase activity	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
viral process	1
viral life cycle	1
exit from host cell	1
blood coagulation	1
granulocyte chemotaxis	1
neutrophil migration	1
leukocyte migration	1
cell chemotaxis	1
activation of protein kinase activity	1
regulation of stress-activated MAPK cascade	1
negative regulation of MAPK cascade	1
stress-activated MAPK cascade	1
negative regulation of stress-activated protein kinase signaling cascade	1
organelle organization	1
response to oxidative stress	1
cellular response to chemical stress	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
regulation of viral life cycle	1
regulation of viral genome replication	1
positive regulation of viral process	1
protein secretion	1
regulation of protein secretion	1
positive regulation of protein transport	1
positive regulation of secretion by cell	1
nucleic acid binding	1
cis-trans isomerase activity	1
catalytic activity, acting on a protein	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
protein binding	1
glycosaminoglycan binding	1
carboxylic acid binding	1
sulfur compound binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 33 of 47 annotations. The rest are phylogenetic / computational / electronic (IEA).

33 experimentally-supported GO terms:

GO term	NS	Evidence
activation of protein kinase B activity	BP	direct assay
apoptotic process	BP	direct assay
cell adhesion molecule production	BP	direct assay
cellular response to oxidative stress	BP	direct assay
endothelial cell activation	BP	direct assay
leukocyte chemotaxis	BP	mutant phenotype
lipid droplet organization	BP	mutant phenotype
negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway	BP	mutant phenotype
negative regulation of protein K48-linked ubiquitination	BP	mutant phenotype
negative regulation of protein kinase activity	BP	direct assay
negative regulation of protein phosphorylation	BP	direct assay
negative regulation of stress-activated MAPK cascade	BP	mutant phenotype
negative regulation of viral life cycle	BP	mutant phenotype
neutrophil chemotaxis	BP	direct assay
positive regulation of MAPK cascade	BP	direct assay
positive regulation of protein phosphorylation	BP	direct assay
positive regulation of protein secretion	BP	mutant phenotype
positive regulation of viral genome replication	BP	mutant phenotype
protein peptidyl-prolyl isomerization	BP	direct assay
regulation of apoptotic signaling pathway	BP	mutant phenotype
regulation of viral genome replication	BP	mutant phenotype
cytoplasm	CC	direct assay
cytosol	CC	high-throughput assay
extracellular exosome	CC	high-throughput assay
extracellular region	CC	direct assay
focal adhesion	CC	high-throughput assay
membrane	CC	high-throughput assay
nucleus	CC	direct assay
protein-containing complex	CC	direct assay
vesicle	CC	high-throughput assay
RNA binding	MF	high-throughput assay
heparan sulfate binding	MF	direct assay
peptidyl-prolyl cis-trans isomerase activity	MF	direct assay

Protein interactions and networks

IntAct

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

showing 30 of 34 partners by confidence:

Partner	Interaction type	MIscore	Records
N	direct interaction	0.710	7
APP	physical association	0.670	3
CRK	direct interaction	0.600	4
BSG	physical association	0.590	2
CDK5	physical association	0.560	3
HCRTR2	physical association	0.560	3
LNX1	physical association	0.560	3
NCOR1	physical association	0.560	3
RPS15	physical association	0.560	3
KMT2D	direct interaction	0.560	2
PTPRN	physical association	0.510	3
SUPT5H	physical association	0.510	2
AIFM1	colocalization	0.460	2
PTCH1	direct interaction	0.440	1
SPHK2	direct interaction	0.440	1
SRPK1	phosphorylation reaction	0.440	1
SRPK2	phosphorylation reaction	0.440	1
BPY2C	physical association	0.400	1
KLB	physical association	0.400	1
M	physical association	0.400	1
MACO1	physical association	0.400	1
PCNA	physical association	0.400	1
PPIF	physical association	0.400	1
USP47	physical association	0.400	1
YWHAZ	physical association	0.400	1
PB2	physical association	0.370	1
PRR13	physical association	0.370	1
ZYX	physical association	0.370	1
COL1A1	association	0.350	1
KLHL15	association	0.350	1

BioGRID (1,128 interactions; top human partners by supporting records in a sample of 600 records): G3BP1 (Affinity Capture-Western; 4 records), USP4 (Affinity Capture-MS; 4 records), AGR2 (Proximity Label-MS; 3 records), BSG (Affinity Capture-MS; 3 records), CTNNB1 (Reconstituted Complex; 3 records), ITK (Co-crystal Structure; 3 records), PARK2 (Affinity Capture-MS; 3 records), PTPRN (Two-hybrid; 3 records), ACE2 (Reconstituted Complex; 2 records), ANKRD36 (Cross-Linking-MS (XL-MS); 2 records), CFL1 (Co-fractionation; 2 records), CSTF3 (Cross-Linking-MS (XL-MS); 2 records), DAXX (Affinity Capture-MS; 2 records), DDX58 (Affinity Capture-Western; 2 records), DMD (Cross-Linking-MS (XL-MS); 2 records)

Protein complexes (CORUM) (7)

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

7 complexes by size:

Complex	Subunits	Members
★ PPIA-PPP3CA-PPP3R1 complex	3	PPIA, PPP3CA, PPP3R1
★ FOXO1-PPIA complex	2	FOXO1, PPIA
★ MAP3K5-PPIA complex	2	MAP3K5, PPIA
★ PPIA-RELA complex	2	PPIA, RELA
★ PPIA-RB1 complex	2	PPIA, RB1
★ PPIA-YY1 complex	2	PPIA, YY1
★ AIFM1-PPIA complex	2	AIFM1, PPIA

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
BSG	ligand

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 34 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Infectious disease	7	7.2×	6e-03

Disease & clinical

Genetic variants

Variant evidence for PPIA: 12 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	5
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 375):

Position(s)	Effect	Δscore	Sites
7:44799693	acceptor_gain	1.0000
7:44799700–44799701	acceptor_loss	1.0000	5
7:44799701	acceptor_gain	1.0000
7:44799875–44799876	donor_loss	1.0000	5
7:44801285	acceptor_gain	1.0000
7:44801286	acceptor_loss	1.0000
7:44796794–44796795	donor_loss	0.9900	3
7:44796830	donor_gain	0.9900
7:44799245–44799246	acceptor_loss	0.9900	6
7:44799691–44799693	acceptor_gain	0.9900	2

AlphaMissense

733 missense substitutions predicted likely pathogenic (of 1,108 scored), across 149 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
M100	9	0.968	0.997
M61	9	0.928	0.993
D66	8	0.996	0.999
D85	8	0.990	0.998
H54	8	0.988	0.998
F60	8	0.986	0.999
H92	8	0.986	0.996
N35	8	0.985	0.998
H126	8	0.983	0.995
F113	8	0.974	0.998
F129	8	0.971	0.994
F83	8	0.969	0.998
N108	8	0.965	0.998
N102	8	0.964	0.997
F112	8	0.964	0.999
F36	8	0.960	0.996
F53	8	0.936	0.995
F88	8	0.925	0.990
F67	8	0.920	0.996
F8	8	0.873	0.975

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

5 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	unfavorable	4.99e-09
Lung Adenocarcinoma (TCGA)	unfavorable	8.07e-06
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	1.91e-05
Pancreatic Adenocarcinoma (TCGA)	unfavorable	6.29e-05
Kidney Renal Clear Cell Carcinoma (validation)	unfavorable	0.000453

Disease associations

OMIM: gene MIM:123840 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
amyotrophic lateral sclerosis	Limited	Autosomal dominant

Mondo (1): amyotrophic lateral sclerosis (MONDO:0004976)

GWAS associations

2 associations:

Study	Trait	p-value
GCST90002396_510	Mean reticulocyte volume	3e-73
GCST90002403_575	Red blood cell count	7e-37

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1949 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the PPIA protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

3 curated-mechanism drugs:

Drug	Modality	Max phase
CYCLOSPORINE	Protein	4
ALISPORIVIR	Protein	3
SCY 635	Protein	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 195,979 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

6 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL160	CYCLOSPORINE	4	169,776
CHEMBL480	LANSOPRAZOLE	4	24,499
CHEMBL1651956	ALISPORIVIR	3	862
CHEMBL1269597	SCY 635	2	584
CHEMBL2107422	GECLOSPORIN	2	89
CHEMBL1688529	NIM811	2	169

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Peptidyl-prolyl cis/trans isomerases

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
CRV431	Inhibition	8.6	pIC50
Sanglifehrin A	Inhibition	8.48	pKd
voclosporin	Binding	7.82	pKd
cyclosporin A	Inhibition	7.76	pKi

Binding affinities (BindingDB)

612 measured of 682 human assays (790 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL6164285	IC50	0.49 nM
[(2S)-2-[(2S,5S,8S,11S,14R,17S,20S,23S,26S,29S,32R)-29-ethyl-26-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,7,11,14,16,19,22,25,31,32-decamethyl-8,17,20-tris(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-5,23-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]propyl] 4-ethylpiperazine-1-carboxylate	KD	0.5 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-24-[(2S)-1-[2-(4-cyclobutylpiperazin-1-yl)ethoxy]propan-2-yl]-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.5 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-24-[(2S)-1-(4-cyclobutylpiperazin-1-yl)propan-2-yl]-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.5 nM	US-9566312: Cyclic peptides and use as medicines
[(2R)-2-[(2S,5S,8S,11S,14R,17S,20S,23S,26S,29S,32R)-29-ethyl-26-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,7,11,14,16,19,22,25,31,32-decamethyl-8,17,20-tris(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-5,23-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]propyl] 4-ethylpiperazine-1-carboxylate	KD	0.5 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-24-[(2S)-1-[2-(4-propan-2-ylpiperazin-1-yl)ethoxy]propan-2-yl]-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.6 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-24-[(2S)-1-[2-[(3S)-3-methoxypyrrolidin-1-yl]ethoxy]propan-2-yl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.6 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-24-[(2S)-1-[2-(3-methoxyazetidin-1-yl)ethoxy]propan-2-yl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.6 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-24-[(2S)-1-morpholin-4-ylpropan-2-yl]-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.6 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-24-[(2S)-1-(4-ethylpiperazin-1-yl)propan-2-yl]-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.6 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-24-[(2S)-1-(3-oxo-5,6,8,8a-tetrahydro-1H-[1,3]oxazolo[3,4-a]pyrazin-7-yl)propan-2-yl]-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.6 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-24-[(2R)-5-(4-ethylpiperazin-1-yl)pentan-2-yl]-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.6 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-24-[(2S)-1-[(4-propan-2-ylmorpholin-2-yl)methoxy]propan-2-yl]-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.6 nM	US-9566312: Cyclic peptides and use as medicines
[(2S)-2-[(2S,5S,8S,11S,14R,17S,20S,23S,26S,29S,32R)-29-ethyl-26-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,7,11,14,16,19,22,25,31,32-decamethyl-8,17,20-tris(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-5,23-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]propyl] N-methyl-N-(1-methylpiperidin-4-yl)carbamate	KD	0.7 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-24-[(2S)-1-[4-(oxetan-3-yl)piperazin-1-yl]propan-2-yl]-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.7 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-24-[(2R)-5-(4-methoxypiperidin-1-yl)pentan-2-yl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.7 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-24-[(2R)-5-[4-(2-methoxyethyl)piperazin-1-yl]pentan-2-yl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.7 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-24-[(2S)-1-[[(2S)-4-ethylmorpholin-2-yl]methoxy]propan-2-yl]-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.7 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33R)-30-ethyl-33-[(1R,2R)-1-hydroxy-5-(5-methoxy-2-pyridinyl)-2-methylpentyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KI	0.72 nM	US-10077289: Cyclosporins modified on the MeBmt sidechain by heterocyclic rings
[(2S)-2-[(2S,5S,8S,11S,14R,17S,20S,23S,26S,29S,32R)-29-ethyl-26-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,7,11,14,16,19,22,25,31,32-decamethyl-8,17,20-tris(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-5,23-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]propyl] 4-methylpiperazine-1-carboxylate	KD	0.8 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-24-[(2R)-5-(8-methyl-3,8-diazabicyclo[3.2.1]octan-3-yl)pentan-2-yl]-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.8 nM	US-9566312: Cyclic peptides and use as medicines
[(4R)-4-[(2S,5S,8S,11S,14R,17S,20S,23S,26S,29S,32R)-29-ethyl-26-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,7,11,14,16,19,22,25,31,32-decamethyl-8,17,20-tris(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-5,23-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]pentyl] N-(1-methylpiperidin-4-yl)carbamate	KD	0.8 nM	US-9566312: Cyclic peptides and use as medicines
[(4R)-4-[(2S,5S,8S,11S,14R,17S,20S,23S,26S,29S,32R)-29-ethyl-26-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,7,11,14,16,19,22,25,31,32-decamethyl-8,17,20-tris(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-5,23-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]pentyl] N-methyl-N-(1-methylpiperidin-4-yl)carbamate	KD	0.8 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-24-[(2R)-1-(4-ethylpiperazin-1-yl)propan-2-yl]-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.9 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-24-[(2S)-1-[2-[(2R,5R)-2,5-dimethylmorpholin-4-yl]ethoxy]propan-2-yl]-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.9 nM	US-9566312: Cyclic peptides and use as medicines
2-[(2S)-2-[(2S,5S,8S,11S,14R,17S,20S,23S,29S,32R)-29-ethyl-26-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,7,11,14,16,19,22,25,31,32-decamethyl-8,17,20-tris(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-5,23-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]propoxy]ethyl 4-methylpiperazine-1-carboxylate	KD	0.9 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(1R,2R)-1-hydroxy-2-methylhexyl]-24-[(2S)-1-[4-(2-methoxyethyl)piperazin-1-yl]propan-2-yl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.9 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-24-[(2S)-1-(4-methylsulfonylpiperazin-1-yl)propan-2-yl]-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.9 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-24-[(2R)-4-[4-(2-methoxyethyl)piperazin-1-yl]butan-2-yl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.9 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-24-[(2R)-4-(3-methoxyazetidin-1-yl)butan-2-yl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.9 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-24-[(2R)-4-piperidin-1-ylbutan-2-yl]-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.9 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-24-[(2R)-5-morpholin-4-ylpentan-2-yl]-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	0.9 nM	US-9566312: Cyclic peptides and use as medicines
1-[(4R)-4-[(2S,5S,8S,11S,14R,17S,20S,23S,26S,29S,32R)-29-ethyl-26-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,7,11,14,16,19,22,25,31,32-decamethyl-8,17,20-tris(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-5,23-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]pentyl]piperidine-4-carboxamide	KD	0.9 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-24-[(2R)-1-(4-propan-2-ylpiperazin-1-yl)propan-2-yl]-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	1 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-24-[(2R)-1-(4-cyclobutylpiperazin-1-yl)propan-2-yl]-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	1 nM	US-9566312: Cyclic peptides and use as medicines
(E,2S,3R,4R)-3-hydroxy-4-methyl-2-[methyl-[(2S)-3-methyl-2-[methyl-[(2S)-4-methyl-2-[methyl-[(2S)-4-methyl-2-[methyl-[(2R)-2-[[(2S)-2-[[(2S)-4-methyl-2-[methyl-[(2S)-3-methyl-2-[[(2S,3S)-3-methyl-2-(methylamino)-4-(2-oxo-2-piperazin-1-ylethoxy)butanoyl]amino]butanoyl]amino]pentanoyl]amino]propanoyl]amino]propanoyl]amino]pentanoyl]amino]pentanoyl]amino]butanoyl]amino]-N-[(2S)-1-[methyl-[(2R)-3-oxobutan-2-yl]amino]-1-oxobutan-2-yl]oct-6-enamide	KD	1 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-24-[(2S)-1-[(3S)-oxolan-3-yl]oxypropan-2-yl]-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	1 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-24-[(2R)-1-(2-oxa-7-azaspiro[3.4]octan-7-yl)propan-2-yl]-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	1.1 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-24-[(2S)-1-[(2S)-2-(methoxymethyl)morpholin-4-yl]propan-2-yl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	1.1 nM	US-9566312: Cyclic peptides and use as medicines
1-[(3R)-3-[(2S,5S,8S,11S,14R,17S,20S,23S,26S,29S,32R)-29-ethyl-26-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,7,11,14,16,19,22,25,31,32-decamethyl-8,17,20-tris(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-5,23-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]butyl]piperidine-4-carbonitrile	KD	1.1 nM	US-9566312: Cyclic peptides and use as medicines
[(4R)-4-[(2S,5S,8S,11S,14R,17S,20S,23S,26S,29S,32R)-29-ethyl-26-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,7,11,14,16,19,22,25,31,32-decamethyl-8,17,20-tris(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-5,23-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]pentyl] 4-methylpiperazine-1-carboxylate	KD	1.1 nM	US-9566312: Cyclic peptides and use as medicines
CHEMBL3344503	KD	1.1 nM
CHEMBL3344502	KD	1.1 nM
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-24-[(2R)-1-[4-(2-methoxyethyl)piperazin-1-yl]propan-2-yl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	1.2 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-24-[(2R)-4-[(3S)-3-methylmorpholin-4-yl]butan-2-yl]-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	1.2 nM	US-9566312: Cyclic peptides and use as medicines
(5S,11S,14S,18E)-14-[(4-hydroxyphenyl)methyl]-2,11,17,17-tetramethyl-15-oxa-2,3,9,12,26,29-hexazatetracyclo[18.5.3.15,9.023,27]nonacosa-1(26),18,20(28),21,23(27),24-hexaene-4,10,13,16-tetrone	IC50	1.2 nM	US-20250243219: MACROCYCLIC COMPOUNDS AND USES THEREOF
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-24-[(2R)-1-[(2S)-2-(methoxymethyl)morpholin-4-yl]propan-2-yl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	1.3 nM	US-9566312: Cyclic peptides and use as medicines
(E,2S,3R,4R)-3-hydroxy-4-methyl-2-[methyl-[(2S)-3-methyl-2-[methyl-[(2S)-4-methyl-2-[methyl-[(2S)-4-methyl-2-[methyl-[(2R)-2-[[(2S)-2-[[(2S)-4-methyl-2-[methyl-[(2S)-3-methyl-2-[[(2S,3S)-3-methyl-2-(methylamino)-4-[2-[4-(oxan-4-yl)piperazin-1-yl]-2-oxoethoxy]butanoyl]amino]butanoyl]amino]pentanoyl]amino]propanoyl]amino]propanoyl]amino]pentanoyl]amino]pentanoyl]amino]butanoyl]amino]-N-[(2S)-1-[methyl-[(2R)-3-oxobutan-2-yl]amino]-1-oxobutan-2-yl]oct-6-enamide	KD	1.3 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-24-[(2S)-1-[2-[(3S)-3-methylmorpholin-4-yl]ethoxy]propan-2-yl]-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	1.3 nM	US-9566312: Cyclic peptides and use as medicines
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-24-[(2S)-1-[2-[(8aS)-3-oxo-5,6,8,8a-tetrahydro-1H-[1,3]oxazolo[3,4-a]pyrazin-7-yl]ethoxy]propan-2-yl]-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	KD	1.3 nM	US-9566312: Cyclic peptides and use as medicines

ChEMBL bioactivities

501 potent at pChembl≥5 of 536 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.51	IC50	0.31	nM	CHEMBL3704747
9.47	Ki	0.34	nM	ALISPORIVIR
9.31	IC50	0.49	nM	CHEMBL6164285
9.30	Kd	0.5	nM	CHEMBL5812164
9.30	Kd	0.5	nM	CHEMBL5792144
9.30	Kd	0.5	nM	CHEMBL6051666
9.30	Kd	0.5	nM	CHEMBL5759368
9.22	Kd	0.6	nM	CHEMBL5791301
9.22	Kd	0.6	nM	CHEMBL5994784
9.22	Kd	0.6	nM	CHEMBL6062788
9.22	Kd	0.6	nM	CHEMBL5810211
9.22	Kd	0.6	nM	CHEMBL5942857
9.22	Kd	0.6	nM	CHEMBL3344501
9.22	Kd	0.6	nM	CHEMBL6010886
9.22	Kd	0.6	nM	CHEMBL6059588
9.22	Kd	0.6	nM	CHEMBL5856868
9.15	Kd	0.7	nM	CHEMBL6056488
9.15	Kd	0.7	nM	CHEMBL6003202
9.15	Kd	0.7	nM	CHEMBL5757514
9.15	Kd	0.7	nM	CHEMBL5866658
9.15	Kd	0.7	nM	CHEMBL6026994
9.14	Ki	0.72	nM	CHEMBL5842028
9.10	IC50	0.8	nM	CHEMBL3704745
9.10	Kd	0.8	nM	CHEMBL5831563
9.10	Kd	0.8	nM	CHEMBL5842043
9.10	Kd	0.8	nM	CHEMBL6048373
9.10	Kd	0.8	nM	CHEMBL5741417
9.05	Kd	0.9	nM	CHEMBL5985508
9.05	Kd	0.9	nM	CHEMBL5967576
9.05	Kd	0.9	nM	CHEMBL5992700
9.05	Kd	0.9	nM	CHEMBL6038296
9.05	Kd	0.9	nM	CHEMBL5976250
9.05	Kd	0.9	nM	CHEMBL5867542
9.05	Kd	0.9	nM	CHEMBL6023421
9.05	Kd	0.9	nM	CHEMBL5812196
9.05	Kd	0.9	nM	CHEMBL6058387
9.05	Kd	0.9	nM	CHEMBL6044098
9.00	Kd	1	nM	CHEMBL5974662
9.00	Kd	1	nM	CHEMBL6062808
9.00	Kd	1	nM	CHEMBL5821248
9.00	Kd	1	nM	CHEMBL5798116
8.96	IC50	1.1	nM	CHEMBL3220760
8.96	Kd	1.1	nM	CHEMBL3344503
8.96	Kd	1.1	nM	CHEMBL3344502
8.96	Kd	1.1	nM	CHEMBL6023618
8.96	Kd	1.1	nM	CHEMBL5960352
8.96	Kd	1.1	nM	CHEMBL5859080
8.96	Kd	1.1	nM	CHEMBL6018548
8.92	Kd	1.2	nM	CHEMBL3344501
8.92	Kd	1.2	nM	CHEMBL5744117

PubChem BioAssay actives

332 with measured affinity, of 732 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
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-25,30-diethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,27,28-nonamethyl-6,9,18-tris(2-methylpropyl)-3,21,24-tri(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	581778: Inhibition of human recombinant cyclophilin-associted cis-trans propyl isomerase activity	ki	0.0003	uM
(3S,6S,9R,10R,11S,12S,13E,15E,18S,21S)-18-[(2E,4E,8S,9S)-10-[(2S,3R,4S,5S,6R,9S,11S)-9-ethyl-4-hydroxy-3,5,11-trimethyl-8-oxo-1-oxa-7-azaspiro[5.5]undecan-2-yl]-9-hydroxy-8-methyldeca-2,4-dien-2-yl]-3-[(3-fluoro-5-hydroxyphenyl)methyl]-10,12-dihydroxy-11-methyl-9-(3-oxobutyl)-6-propan-2-yl-19-oxa-1,4,7,25-tetrazabicyclo[19.3.1]pentacosa-13,15-diene-2,5,8,20-tetrone	2233939: Inhibition of PPIA (unknown origin) using N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide as substrate preincubated for 1 hr followed by substrate addition measured for 6 mins by absorbance based assay	ic50	0.0005	uM
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-24-[(2R)-4-morpholin-4-ylbutan-2-yl]-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	1168824: Binding affinity to human cyclophilin A by surface plasmon resonance method	kd	0.0011	uM
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-24-[(2S)-1-(2-morpholin-4-ylethoxy)propan-2-yl]-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	1168824: Binding affinity to human cyclophilin A by surface plasmon resonance method	kd	0.0011	uM
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-24-[(2S)-1-[4-(2-methoxyethyl)piperazin-1-yl]propan-2-yl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	1168824: Binding affinity to human cyclophilin A by surface plasmon resonance method	kd	0.0012	uM
(3R)-3-[(2S,5S,8S,11S,14R,17S,20S,23S,26S,29S,32R)-29-ethyl-26-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,7,11,14,16,19,22,25,31,32-decamethyl-8,17,20-tris(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-5,23-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]butanenitrile	1168824: Binding affinity to human cyclophilin A by surface plasmon resonance method	kd	0.0013	uM
1-[(2R)-2-[(2S,5S,8S,11S,14R,17S,20S,23S,26S,29S,32R)-29-ethyl-26-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,7,11,14,16,19,22,25,31,32-decamethyl-8,17,20-tris(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-5,23-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]propyl]piperidine-4-carbonitrile	1168824: Binding affinity to human cyclophilin A by surface plasmon resonance method	kd	0.0014	uM
2-chloro-N-(9H-fluoren-9-ylcarbamoyl)-6-fluorobenzamide	427507: Inhibition of peptidyl-prolyl isomerase activity of Cyclophilin A	ic50	0.0015	uM
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-24-[(2S)-1-methoxypropan-2-yl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	1168824: Binding affinity to human cyclophilin A by surface plasmon resonance method	kd	0.0017	uM
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-27-[2-(dimethylamino)ethylsulfanyl]-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-24-(2-hydroxy-2-methylpropyl)-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	2233938: Inhibition of PPIA (unknown origin)	ki	0.0018	uM
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-24-[(2R)-1-[2-methoxyethyl(methyl)amino]propan-2-yl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	1168824: Binding affinity to human cyclophilin A by surface plasmon resonance method	kd	0.0018	uM
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-24-[(2R)-1-(1,4-oxazepan-4-yl)propan-2-yl]-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	1168824: Binding affinity to human cyclophilin A by surface plasmon resonance method	kd	0.0019	uM
cyclosporine	95464: Immunosuppressive activity was measured by inhibition of the IL-2 production in Jurkat cells.	ic50	0.0020	uM
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-24-[(2S)-butan-2-yl]-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	2233938: Inhibition of PPIA (unknown origin)	ki	0.0021	uM
(3S,6S,9S,12R,15S,18S,21S,24S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-24-[(2S)-2-methylbutyl]-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	54723: Compound was evaluated for in vitro binding affinity to cyclophilin A (CyP-A)	ic50	0.0023	uM
N-[(7R,8R)-8-[(2S,5S,8R,11S,14S,17S,20S,23R,26S,29S,32S)-5-ethyl-1,7,8,10,16,20,23,25,28,31-decamethyl-11,17,26,29-tetrakis(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-14,32-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]-8-hydroxy-7-methyloctyl]acetamide;methane	2233938: Inhibition of PPIA (unknown origin)	ki	0.0025	uM
N-(9H-fluoren-9-ylcarbamoyl)-2,6-dihydroxybenzamide	427507: Inhibition of peptidyl-prolyl isomerase activity of Cyclophilin A	kd	0.0025	uM
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-24-[(2R)-1-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)propan-2-yl]-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	1168824: Binding affinity to human cyclophilin A by surface plasmon resonance method	kd	0.0025	uM
2,6-dichloro-N-(9H-fluoren-9-ylcarbamoyl)benzamide	427507: Inhibition of peptidyl-prolyl isomerase activity of Cyclophilin A	ic50	0.0026	uM
2-[[(2R,5S,8S,11S,14S,17S,23S,26S,29S,32S)-17-ethyl-14-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-4,7,10,13,19,22,28,32-octamethyl-5,8,23,29-tetrakis(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-11,26-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]methoxy]-N-(4-phenyldiazenylphenyl)acetamide	495176: Inhibition of PPIase activity of cyclophilin 18 by protease coupled assay	ic50	0.0028	uM
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-27-methylsulfanyl-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	95464: Immunosuppressive activity was measured by inhibition of the IL-2 production in Jurkat cells.	ic50	0.0030	uM
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-24-[(2R)-1-morpholin-4-ylpropan-2-yl]-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	1168824: Binding affinity to human cyclophilin A by surface plasmon resonance method	kd	0.0031	uM
(3S,6S,9R,10R,11S,12S,13E,15E,18S,21S)-18-[(2E,4E,8S,9S)-10-[(2S,3R,4S,5S,6R,9S,11S)-9-ethyl-4-hydroxy-3,5,11-trimethyl-8-oxo-1-oxa-7-azaspiro[5.5]undecan-2-yl]-9-hydroxy-8-methyldeca-2,4-dien-2-yl]-10,12-dihydroxy-3-[(3-hydroxyphenyl)methyl]-11-methyl-9-(3-oxobutyl)-6-propan-2-yl-19-oxa-1,4,7,25-tetrazabicyclo[19.3.1]pentacosa-13,15-diene-2,5,8,20-tetrone	1362385: Inhibition of Cy5-labeled cyclosporin A binding to full length recombinant human N-terminal His8-tagged Cyclophilin A (1 to 169 residues) expressed in Escherichia coli BL21(DE3) after 30 mins by TR-FRET assay	kd	0.0033	uM
(2R,5S,11S,14S,17R,18R,21E)-11-[(3-hydroxyphenyl)methyl]-18-methoxy-2,17-dimethyl-14-propan-2-yl-3-oxa-9,12,15,28-tetrazatricyclo[21.3.1.15,9]octacosa-1(26),21,23(27),24-tetraene-4,10,13,16-tetrone	1426805: Inhibition of full length recombinant human N-terminal His8-tagged Cyclophilin A (1 to 169 residues) expressed in Escherichia coli BL21(DE3) using Suc-Ala-Ala-Pro-Phe-para-nitroanilide as substrate after 5 mins by spectrophotometric method	ki	0.0040	uM
(2R,5S,11S,14S,18E)-2,11,17,17-tetramethyl-14-propan-2-yl-3-oxa-9,12,15,26,29-pentazatetracyclo[18.5.3.15,9.023,27]nonacosa-1(26),18,20(28),21,23(27),24-hexaene-4,10,13,16-tetrone	1362385: Inhibition of Cy5-labeled cyclosporin A binding to full length recombinant human N-terminal His8-tagged Cyclophilin A (1 to 169 residues) expressed in Escherichia coli BL21(DE3) after 30 mins by TR-FRET assay	kd	0.0040	uM
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-24-[(2R)-1-(3,3-difluoropyrrolidin-1-yl)propan-2-yl]-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,27,28-decamethyl-6,9,18-tris(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	1168824: Binding affinity to human cyclophilin A by surface plasmon resonance method	kd	0.0040	uM
(2R,5S,11S,14S,18E)-4’-hydroxy-2,11-dimethyl-14-propan-2-ylspiro[15-oxa-3,9,12,26,29-pentazatetracyclo[18.5.3.15,9.023,27]nonacosa-1(26),18,20(28),21,23(27),24-hexaene-17,1’-cyclohexane]-4,10,13,16-tetrone	1362385: Inhibition of Cy5-labeled cyclosporin A binding to full length recombinant human N-terminal His8-tagged Cyclophilin A (1 to 169 residues) expressed in Escherichia coli BL21(DE3) after 30 mins by TR-FRET assay	kd	0.0040	uM
(2R,5S,11S,14S,21E)-2,11-dimethyl-14-propan-2-yl-3-oxa-9,12,15,28-tetrazatricyclo[21.3.1.15,9]octacosa-1(26),21,23(27),24-tetraene-4,10,13,16-tetrone	1426805: Inhibition of full length recombinant human N-terminal His8-tagged Cyclophilin A (1 to 169 residues) expressed in Escherichia coli BL21(DE3) using Suc-Ala-Ala-Pro-Phe-para-nitroanilide as substrate after 5 mins by spectrophotometric method	ki	0.0043	uM
(4R)-5-[[(2R)-4-carboxy-1-[[(2R)-4-carboxy-1-[[(2R)-4-carboxy-1-[[(2R)-4-carboxy-1-[[(2R)-4-carboxy-1-(carboxymethylamino)-1-oxobutan-2-yl]amino]-1-oxobutan-2-yl]amino]-1-oxobutan-2-yl]amino]-1-oxobutan-2-yl]amino]-1-oxobutan-2-yl]amino]-4-[3-[(E,5R,6R)-6-[(2S,5S,11S,14S,17S,20S,23R,26S,29S,32S)-5-ethyl-1,7,10,16,20,23,25,28,31-nonamethyl-11,17,26,29-tetrakis(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-14,32-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]-6-hydroxy-5-methylhex-2-enyl]sulfanylpropanoylamino]-5-oxopentanoic acid	625946: Inhibition of PPIase activity of human recombinant cyclophilin-A using succinyl-Ala-Ala-Pro-Phe-4-nitroanilide as substrate by protease coupled assay	ic50	0.0049	uM
(2R,5S,11S,14S,18E)-4’-methoxy-2,11-dimethyl-14-propan-2-ylspiro[15-oxa-3,9,12,26,29-pentazatetracyclo[18.5.3.15,9.023,27]nonacosa-1(26),18,20(28),21,23(27),24-hexaene-17,1’-cyclohexane]-4,10,13,16-tetrone	1362385: Inhibition of Cy5-labeled cyclosporin A binding to full length recombinant human N-terminal His8-tagged Cyclophilin A (1 to 169 residues) expressed in Escherichia coli BL21(DE3) after 30 mins by TR-FRET assay	kd	0.0050	uM
(2R,5S,11S,14S,18E)-2,11,17,17-tetramethyl-14-propan-2-yl-3-oxa-9,12,15,21,29-pentazatetracyclo[18.5.3.15,9.023,27]nonacosa-1(26),18,20,22,24,27-hexaene-4,10,13,16-tetrone	1362385: Inhibition of Cy5-labeled cyclosporin A binding to full length recombinant human N-terminal His8-tagged Cyclophilin A (1 to 169 residues) expressed in Escherichia coli BL21(DE3) after 30 mins by TR-FRET assay	kd	0.0050	uM
(2’R,5’S,11’S,14’S,18’E)-2’,11’-dimethyl-14’-propan-2-ylspiro[1,3-dioxane-5,17’-15-oxa-3,9,12,26,29-pentazatetracyclo[18.5.3.15,9.023,27]nonacosa-1(26),18,20(28),21,23(27),24-hexaene]-4’,10’,13’,16’-tetrone	1362385: Inhibition of Cy5-labeled cyclosporin A binding to full length recombinant human N-terminal His8-tagged Cyclophilin A (1 to 169 residues) expressed in Escherichia coli BL21(DE3) after 30 mins by TR-FRET assay	kd	0.0050	uM
N-cyclohexyl-2-(N-[2-(1H-indol-3-yl)acetyl]-4-propan-2-ylanilino)-2-(3,4,5-trimethoxyphenyl)acetamide	1271174: Inhibition of Cyclophilin A peptidyl-prolyl cis-trans isomerase activity (unknown origin) using Succ-Ala-Leu-Pro-Phe-p-nitroaniline as substrate by ITC analysis	ic50	0.0055	uM
(2’R,5’S,11’S,14’S,18’E)-14’-cyclobutyl-2’,11’-dimethylspiro[1,3-dioxane-5,17’-15-oxa-3,9,12,26,29-pentazatetracyclo[18.5.3.15,9.023,27]nonacosa-1(26),18,20(28),21,23(27),24-hexaene]-4’,10’,13’,16’-tetrone	2205593: Binding affinity to cyclophilin A (unknown origin) assessed as inhibition constant incubated for 30 mins by fluorescence polarization assay	ki	0.0060	uM
1-[[(1R,9R,10S)-10-hydroxy-1,9-dimethyl-12-oxa-8-azatricyclo[7.3.1.02,7]trideca-2(7),3,5-trien-4-yl]methyl]-3-[2-[(2R)-2-(2-methylsulfanylphenyl)pyrrolidin-1-yl]-2-oxoethyl]-1-[(2-methyltetrazol-5-yl)methyl]urea	2235543: Binding affinity to human full length N-terminal CypA (1 to 165 residues) extracted from Escherichia coli BL21 (DE3) cells assessed as dissociation constant by SPR method	kd	0.0060	uM
(2R,5S,11S,14S,17R,18R,21E)-18-methoxy-2,11,17-trimethyl-14-propan-2-yl-3-oxa-9,12,15,28-tetrazatricyclo[21.3.1.15,9]octacosa-1(26),21,23(27),24-tetraene-4,10,13,16-tetrone	1426805: Inhibition of full length recombinant human N-terminal His8-tagged Cyclophilin A (1 to 169 residues) expressed in Escherichia coli BL21(DE3) using Suc-Ala-Ala-Pro-Phe-para-nitroanilide as substrate after 5 mins by spectrophotometric method	ki	0.0070	uM
(2’R,5’S,11’S,14’S,18’E)-2’,11’-dimethyl-14’-propan-2-ylspiro[1,4-dioxepane-6,17’-15-oxa-3,9,12,26,29-pentazatetracyclo[18.5.3.15,9.023,27]nonacosa-1(26),18,20(28),21,23(27),24-hexaene]-4’,10’,13’,16’-tetrone	1362385: Inhibition of Cy5-labeled cyclosporin A binding to full length recombinant human N-terminal His8-tagged Cyclophilin A (1 to 169 residues) expressed in Escherichia coli BL21(DE3) after 30 mins by TR-FRET assay	kd	0.0080	uM
(3S,6S,9S,15S,18S,21S,24S,27S,30R,33S)-15-ethyl-18-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-4,10,13,19,22,25,28,30,33-nonamethyl-3,9,24,27-tetrakis(2-methylpropyl)-6,21-di(propan-2-yl)-32-sulfanylidene-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29-decone	1331002: Binding affinity to Cyp18 (unknown origin) by fluorescence assay	kd	0.0082	uM
(2R,5S,11S,14S,18E)-2,11,17,17-tetramethyl-14-propan-2-yl-15-oxa-3,9,12,26,29-pentazatetracyclo[18.5.3.15,9.023,27]nonacosa-1(26),18,20(28),21,23(27),24-hexaene-4,10,13,16-tetrone	1362385: Inhibition of Cy5-labeled cyclosporin A binding to full length recombinant human N-terminal His8-tagged Cyclophilin A (1 to 169 residues) expressed in Escherichia coli BL21(DE3) after 30 mins by TR-FRET assay	kd	0.0090	uM
2-[(2R,5S,8S,11S,14S,17S,23S,26S,29S,32S)-17-ethyl-14-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-4,7,10,13,19,22,28,32-octamethyl-5,8,23,29-tetrakis(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-11,26-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]acetonitrile	528322: Binding affinity to cyclophilin A by ELISA	ic50	0.0091	uM
(2R,5S,11S,14S,18E)-2,11,17,17-tetramethyl-14-propan-2-yl-15-oxa-3,9,12,21,29-pentazatetracyclo[18.5.3.15,9.023,27]nonacosa-1(26),18,20,22,24,27-hexaene-4,10,13,16-tetrone	1362385: Inhibition of Cy5-labeled cyclosporin A binding to full length recombinant human N-terminal His8-tagged Cyclophilin A (1 to 169 residues) expressed in Escherichia coli BL21(DE3) after 30 mins by TR-FRET assay	kd	0.0100	uM
(3S,6S,9R,12R,15S,18S,21R,24R,30S,33S)-30-ethyl-33-[(E,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	238355: Inhibition of cyclophilin A rotamase	ki	0.0100	uM
(2R,5S,11S,14S,18E)-2,11-dimethyl-14-propan-2-yl-3-oxa-9,12,15,21,29-pentazatetracyclo[18.5.3.15,9.023,27]nonacosa-1(26),18,20,22,24,27-hexaene-4,10,13,16-tetrone	1362385: Inhibition of Cy5-labeled cyclosporin A binding to full length recombinant human N-terminal His8-tagged Cyclophilin A (1 to 169 residues) expressed in Escherichia coli BL21(DE3) after 30 mins by TR-FRET assay	kd	0.0100	uM
2-[(2R,3R)-3-[(2S,5S,11S,14S,17S,20S,23R,26S,29S,32S)-5-ethyl-1,7,10,16,20,23,25,28,31-nonamethyl-11,17,26,29-tetrakis(2-methylpropyl)-3,6,9,12,15,18,21,24,27,30,33-undecaoxo-14,32-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacont-2-yl]-3-hydroxy-2-methylpropyl]-3H-benzimidazole-5-carboxylic acid	770489: Inhibition of CypA PPIase activity (unknown origin) using Glt-(Ala)n-Pro-Phe-4-nitroanilides as substrate	ki	0.0107	uM
(2R,5S,11S,14S,18E)-2,11-dimethyl-14-propan-2-ylspiro[15-oxa-3,9,12,26,29-pentazatetracyclo[18.5.3.15,9.023,27]nonacosa-1(26),18,20(28),21,23(27),24-hexaene-17,4’-oxane]-4,10,13,16-tetrone	1362385: Inhibition of Cy5-labeled cyclosporin A binding to full length recombinant human N-terminal His8-tagged Cyclophilin A (1 to 169 residues) expressed in Escherichia coli BL21(DE3) after 30 mins by TR-FRET assay	kd	0.0110	uM
(2R,5S,11S,14S,18E)-17,17-bis(hydroxymethyl)-2,11-dimethyl-14-propan-2-yl-15-oxa-3,9,12,26,29-pentazatetracyclo[18.5.3.15,9.023,27]nonacosa-1(26),18,20(28),21,23(27),24-hexaene-4,10,13,16-tetrone	1362385: Inhibition of Cy5-labeled cyclosporin A binding to full length recombinant human N-terminal His8-tagged Cyclophilin A (1 to 169 residues) expressed in Escherichia coli BL21(DE3) after 30 mins by TR-FRET assay	kd	0.0110	uM
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-9,18,24-tris(2-methylpropyl)-3,6,21-tri(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	719606: Binding affinity to human cyclophilin A by fluorescence polarization assay	kd	0.0110	uM
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-7,30-diethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,10,12,15,19,25,28-octamethyl-9,18,24-tris(2-methylpropyl)-3,6,21-tri(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	719606: Binding affinity to human cyclophilin A by fluorescence polarization assay	kd	0.0110	uM
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-12-(4-aminobutyl)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,15,19,25,28-octamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone	528322: Binding affinity to cyclophilin A by ELISA	ic50	0.0111	uM
N-(4-bromophenyl)-N-[2-(cyclohexylamino)-1-(4-nitrophenyl)-2-oxoethyl]-3-(4-methoxyphenyl)propanamide	1271174: Inhibition of Cyclophilin A peptidyl-prolyl cis-trans isomerase activity (unknown origin) using Succ-Ala-Leu-Pro-Phe-p-nitroaniline as substrate by ITC analysis	ic50	0.0112	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation, affects cotreatment, affects expression, decreases expression	4
sodium arsenite	decreases expression, increases expression	3
Cisplatin	affects binding, decreases response to substance, increases expression	3
Copper	affects binding, decreases expression	3
Tobacco Smoke Pollution	increases metabolic processing, affects expression, increases expression	3
Cyclosporine	decreases expression, increases expression	3
torcetrapib	increases expression	2
Arsenic Trioxide	increases expression	2
Quercetin	increases expression	2
Valproic Acid	affects expression, decreases expression	2
Zinc	decreases expression	2
Okadaic Acid	decreases expression, increases expression	2
bisphenol F	affects cotreatment, decreases expression	1
uranyl acetate	affects expression	1
chlorophyllin	increases expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment, affects localization	1
trichostatin A	affects cotreatment, decreases expression	1
ferric ammonium citrate	decreases reaction, increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	increases expression	1
zinc chromate	increases abundance, increases expression	1
nickel sulfate	affects expression	1
artenimol	affects binding	1
Bandrowski’s base	affects expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
K 7174	decreases expression	1
indioside D	decreases expression	1

ChEMBL screening assays

155 unique, capped per target: 154 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1012281	Binding	Binding affinity to human Cyclophilin A	Simultaneous identification of multiple receptors of natural product using an optimized cDNA phage display cloning. — *Bioorg Med Chem Lett*
CHEMBL701785	Functional	Immunosuppressive activity was measured by inhibition of the IL-2 production in Jurkat cells.	Synthesis of non-immunosuppressive cyclophilin-Binding cyclosporin A derivatives as potential anti-HIV-1 drugs. — *Bioorg Med Chem Lett*

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1H23	PPIA-/- Jurkat	Cancer cell line	Male
CVCL_F6F6	EDITGENE PPIA Knockout NALM6, clone G5 Cell Line	Cancer cell line	Male

Clinical trials (associated diseases)

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

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00542412	Phase 4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00560287	Phase 4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00613899	Phase 4	COMPLETED	Feasibility of Telesurveillance and Home Cough Assistance for Amyotrophic Lateral Patients (ALS)
NCT04997954	Phase 4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT06849115	Phase 4	COMPLETED	Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations
NCT07223723	Phase 4	ACTIVE_NOT_RECRUITING	A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS)
NCT00021697	Phase 3	COMPLETED	Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
NCT00035815	Phase 3	COMPLETED	Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
NCT00047723	Phase 3	COMPLETED	Minocycline to Treat Amyotrophic Lateral Sclerosis
NCT00069186	Phase 3	UNKNOWN	Study of Creatine Monohydrate in Patients With Amyotrophic Lateral Sclerosis
NCT00136110	Phase 3	COMPLETED	Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis
NCT00330681	Phase 3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS)
NCT00349622	Phase 3	COMPLETED	Clinical Trial Ceftriaxone in Subjects With ALS
NCT00372879	Phase 3	COMPLETED	Clinical Trial of Vitamin E to Treat Muscular Cramps in Patients With ALS
NCT00415519	Phase 3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS) Who Met Severity Classification III
NCT00424463	Phase 3	COMPLETED	Expanded Controlled Study of Safety and Efficacy of MCI-186 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT00839033	Phase 3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00868166	Phase 3	COMPLETED	Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS
NCT00965497	Phase 3	COMPLETED	Escitalopram (Lexapro) for Depression MS or ALS
NCT01016522	Phase 3	TERMINATED	Safety and Tolerability of the Ketogenic Diet in Amyotrophic Lateral Sclerosis (ALS)
NCT01160263	Phase 3	COMPLETED	Study of Dopamine and Serotonin Transporters in Patients With Amyotrophic Lateral Sclerosis and Controls
NCT01281189	Phase 3	COMPLETED	Phase 3 Study of Dexpramipexole in ALS
NCT01492686	Phase 3	COMPLETED	Phase 3 Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis
NCT01583088	Phase 3	TERMINATED	Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation
NCT01622088	Phase 3	TERMINATED	Phase 3 Extension Study of Dexpramipexole in ALS
NCT02496767	Phase 3	COMPLETED	Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year
NCT02623699	Phase 3	COMPLETED	An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)
NCT02936635	Phase 3	COMPLETED	A Study for Patients Who Completed VITALITY-ALS (CY 4031)
NCT03127267	Phase 3	RECRUITING	Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
NCT03280056	Phase 3	COMPLETED	Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients
NCT03491462	Phase 3	COMPLETED	Arimoclomol in Amyotropic Lateral Sclerosis
NCT03505021	Phase 3	COMPLETED	Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS
NCT03548311	Phase 3	COMPLETED	Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
NCT03690791	Phase 3	UNKNOWN	Efficacy of Cannabinoids in Amyotrophic Lateral Sclerosis or Motor Neurone Disease
NCT03800524	Phase 3	UNKNOWN	Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS
NCT03836716	Phase 3	TERMINATED	Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
NCT03948178	Phase 3	TERMINATED	Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
NCT04165824	Phase 3	COMPLETED	Safety Study of Oral Edaravone Administered in Subjects With ALS
NCT04248465	Phase 3	TERMINATED	An Efficacy and Safety Study of Ravulizumab in ALS Participants
NCT04569084	Phase 3	TERMINATED	Efficacy and Safety Study of Oral Edaravone Administered in Subjects With ALS
NCT04577404	Phase 3	COMPLETED	Safety Extension Study of Oral Edaravone Administered in Subjects With Amyotrophic Lateral Sclerosis (ALS)
NCT04745299	Phase 3	COMPLETED	Evaluation the Efficacy and Safety of Mutiple Lenzumestrocel (Neuronata-R® Inj.) Treatment in Patients With ALS
NCT04768972	Phase 3	ACTIVE_NOT_RECRUITING	FUSION: A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of ION363 in Amyotrophic Lateral Sclerosis Participants With Fused in Sarcoma Mutations (FUS-ALS)
NCT04944784	Phase 3	TERMINATED	A Study to Evaluate the Efficacy and Safety of Reldesemtiv in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT05021536	Phase 3	UNKNOWN	Phase III Trial of AMX0035 for Amyotrophic Lateral Sclerosis Treatment
NCT05151471	Phase 3	TERMINATED	Efficacy and Safety Extension Study of Oral Edaravone Administered in Subjects With ALS
NCT05178810	Phase 3	COMPLETED	Study to Investigate the Efficacy and Safety of FAB122 (Daily Oral Edaravone) in Patients With Amyotrophic Lateral Sclerosis
NCT05193994	Phase 3	TERMINATED	Triumeq in Amyotrophic Lateral Sclerosis
NCT05442775	Phase 3	TERMINATED	A Phase 3, Open-Label Extension of COURAGE-ALS (CY 5031)
NCT05568615	Phase 3	COMPLETED	Extension Study Following the Studies MT-1186-A03 or A04 to Evaluate the Safety of Oral Edaravone in Subjects With ALS
NCT05619783	Phase 3	COMPLETED	Extension Study Evaluating The Safety And Tolerability of AMX0035
NCT05753852	Phase 3	UNKNOWN	Open Label Extension of TUDCA-ALS Study
NCT05866926	Phase 3	TERMINATED	Study to Investigate the Long-term Safety of FAB122 in Patients With Amyotrophic Lateral Sclerosis
NCT06008249	Phase 3	TERMINATED	Platform Trial to Assess the Efficacy of Multiple Drugs in Amyotrophic Lateral Sclerosis (ALS)
NCT06658977	Phase 3	TERMINATED	RolloverTreatment With Triumeq for People With ALS Following the Lighthouse II Trial
NCT06973629	Phase 3	NOT_YET_RECRUITING	Efficacy and Safety of MSC-NTF (NurOwn) in Participants With Early Symptomatic ALS and Moderate Disease Presentation in ALS (ENDURANCE STUDY)
NCT07174492	Phase 3	NOT_YET_RECRUITING	Efficacy and Safety of Masitinib in Combination With SoC Versus Placebo in the Treatment of ALS Patients
NCT07322003	Phase 3	RECRUITING	Pridopidine Phase 3 Study to Evaluate Efficacy and Safety in ALS
NCT00004771	Phase 2	COMPLETED	Phase II Study of Leuprolide and Testosterone for Men With Kennedy’s Disease or Other Motor Neuron Disease
NCT00005674	Phase 2	COMPLETED	Clinical Trial of Creatine in Amyotrophic Lateral Sclerosis [ALS]

Predicted chemistry — Sugi Predict

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