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
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 80.0% of screened cell lines
• 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: 26 — 17 protein_coding, 5 retained_intron, 4 nonsense_mediated_decay

ENST00000355968, ENST00000415933, ENST00000451562, ENST00000468812, ENST00000479021, ENST00000480603, ENST00000481437, ENST00000489459, ENST00000494484, ENST00000620047, ENST00000676977, ENST00000677022, ENST00000677107, ENST00000677521, ENST00000678165, ENST00000678643, ENST00000678789, ENST00000678805, ENST00000891940, ENST00000915253, ENST00000915254, ENST00000915255, ENST00000915256, ENST00000915257, ENST00000915258, ENST00000915259

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.

FANTOM5 promoters (2 alternative TSS)

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

Top tissues by expression

288 total, 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

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

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

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

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-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

DepMap (CRISPR cell-line fitness): dependent in 80.0% of screened cell lines.

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)

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, F8WE65, P62937, 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), 1 shown:

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

UniProt features (59 total): strand 15, mutagenesis site 13, modified residue 11, turn 5, cross-link 3, sequence conflict 3, helix 3, chain 2, initiator methionine 1, glycosylation site 1, splice variant 1, domain 1

Structure

Experimental structures (PDB)

202 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9E3S	X-RAY DIFFRACTION	1.08
9BG4	X-RAY DIFFRACTION	1.14
4N1M	X-RAY DIFFRACTION	1.15
5F66	X-RAY DIFFRACTION	1.15
9GHY	X-RAY DIFFRACTION	1.15
6GJL	X-RAY DIFFRACTION	1.16
6GS6	X-RAY DIFFRACTION	1.16
2X25	X-RAY DIFFRACTION	1.2
4YUO	X-RAY DIFFRACTION	1.2
7UXM	X-RAY DIFFRACTION	1.2
8TBG	X-RAY DIFFRACTION	1.2
9BFV	X-RAY DIFFRACTION	1.2
9BFW	X-RAY DIFFRACTION	1.2
9BG8	X-RAY DIFFRACTION	1.2
3K0M	X-RAY DIFFRACTION	1.25
5LUD	X-RAY DIFFRACTION	1.25
8TBK	X-RAY DIFFRACTION	1.26
9BFY	X-RAY DIFFRACTION	1.26
9CT8	X-RAY DIFFRACTION	1.28
6GJY	X-RAY DIFFRACTION	1.29
9CTA	X-RAY DIFFRACTION	1.29
9CTB	X-RAY DIFFRACTION	1.29
5NOU	X-RAY DIFFRACTION	1.3
7ABT	X-RAY DIFFRACTION	1.31
9BG3	X-RAY DIFFRACTION	1.33
4YUH	X-RAY DIFFRACTION	1.34
5NOS	X-RAY DIFFRACTION	1.35
9CT9	X-RAY DIFFRACTION	1.35
6GJM	X-RAY DIFFRACTION	1.35
7UXN	X-RAY DIFFRACTION	1.36

Predicted structure (AlphaFold)

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

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): 82, 93, 125, 131, 133, 28, 28, 82, 1, 2, 28, 44, 76, 77

Glycosylation sites (1): 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
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 leuk
70	no effect on peptidyl-prolyl cis-trans isomerase activity. reduced interaction with bsg/cd147 and ability to induce leuk
107	no effect on peptidyl-prolyl cis-trans isomerase activity. reduced interaction with bsg/cd147 and ability to induce leuk
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/er

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-162585	Uncoating of the HIV Virion
R-HSA-162588	Budding and maturation of HIV virion
R-HSA-162592	Integration of provirus
R-HSA-162594	Early Phase of HIV Life Cycle
R-HSA-164516	Minus-strand DNA synthesis
R-HSA-164525	Plus-strand DNA synthesis
R-HSA-173107	Binding and entry of HIV virion
R-HSA-175474	Assembly Of The HIV Virion
R-HSA-180689	APOBEC3G mediated resistance to HIV-1 infection
R-HSA-2025928	Calcineurin activates NFAT
R-HSA-210991	Basigin interactions
R-HSA-6798695	Neutrophil degranulation
R-HSA-8950505	Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation
R-HSA-9692916	SARS-CoV-1 activates/modulates innate immune responses

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 (27): 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), neuron differentiation (GO:0030182), 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), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), 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 (9): 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), obsolete unfolded protein binding (GO:0051082), heparan sulfate binding (GO:1904399), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (12): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), 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

Rollup of top-11 pathways:

Category	Pathways
Early Phase of HIV Life Cycle	3
Late Phase of HIV Life Cycle	2
Reverse Transcription of HIV RNA	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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
regulation of protein phosphorylation	2
protein phosphorylation	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
cellular process	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
cell differentiation	1
generation of neurons	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

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

273 interactions, top by confidence:

A	B	Type	Score
SMARCD1	ARID1A	psi-mi:“MI:0914”(association)	0.790
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
N	PPIA	psi-mi:“MI:0407”(direct interaction)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PPIA	N	psi-mi:“MI:0407”(direct interaction)	0.680
PPIA	N	psi-mi:“MI:0915”(physical association)	0.680
N	PPIA	psi-mi:“MI:0407”(direct interaction)	0.680
APP	PPIA	psi-mi:“MI:0915”(physical association)	0.670
gag	PPIA	psi-mi:“MI:0407”(direct interaction)	0.620
PPIA	gag	psi-mi:“MI:0407”(direct interaction)	0.620
PPIA	CRK	psi-mi:“MI:0407”(direct interaction)	0.600
PPIA	CRK	psi-mi:“MI:2364”(proximity)	0.600
PPIA	BSG	psi-mi:“MI:0915”(physical association)	0.590
BSG	PPIA	psi-mi:“MI:0915”(physical association)	0.590
PPIA	LNX1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (1116): PPIA (Affinity Capture-MS), PPIA (Affinity Capture-MS), TCF4 (Two-hybrid), LNX1 (Two-hybrid), PPIA (Reconstituted Complex), PPIA (Affinity Capture-MS), PPIA (Affinity Capture-MS), PRR13 (Two-hybrid), PPIA (Affinity Capture-MS), PPIA (Affinity Capture-MS), PPIA (Co-fractionation), PPIA (Co-fractionation), PPIA (Co-fractionation), PPIA (Co-fractionation), PPIA (Co-fractionation)

ESM2 similar proteins: A0A075B759, A0A075B767, A0A0B4J2A2, F5H284, O00060, O43447, O74729, P0C1I3, P0C1I5, P0C1I8, P0CP82, P0CP83, P0DN26, P0DN37, P17742, P23285, P24525, P25719, P52010, P52018, P62935, P62937, P62938, P62940, P62941, P84343, Q0P5D0, Q0ZQK6, Q0ZQK7, Q0ZQK8, Q0ZQL0, Q0ZQL1, Q0ZQL2, Q26516, Q26565, Q2TZ33, Q38867, Q38900, Q42406, Q4IPH4

Diamond homologs: A0A075B759, A0A075B767, A0A0B4J2A2, A0A0R0H9T5, A4FV72, D4AY02, F5H284, H2QII6, O00060, O49886, O93826, P0C1H7, P0C1H8, P0C1I2, P0C1I7, P0C1I8, P0C1I9, P0CP78, P0CP79, P0DN26, P0DN37, P10111, P10255, P14088, P14832, P14851, P17742, P18253, P21568, P21569, P22011, P24367, P24525, P25007, P25719, P29117, P30404, P30405, P34790, P34791

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 169 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
Signaling by FLT3 ITD and TKD mutants	5	31.7×	7e-05
Insulin receptor signalling cascade	5	28.0×	9e-05
Signaling by FLT3 fusion proteins	5	23.8×	1e-04
SHC-mediated cascade:FGFR4	5	22.7×	1e-04
FRS-mediated FGFR4 signaling	5	20.7×	1e-04
FCERI mediated MAPK activation	6	17.3×	1e-04
Signaling by high-kinase activity BRAF mutants	6	15.9×	1e-04
Downstream signal transduction	5	15.9×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of long-term neuronal synaptic plasticity	5	35.1×	2e-04
amyloid fibril formation	5	21.3×	8e-04
regulation of nucleotide-excision repair	5	21.3×	8e-04
autophagosome maturation	6	14.9×	8e-04
mitophagy	6	13.5×	1e-03
adult locomotory behavior	5	10.7×	7e-03
Ras protein signal transduction	7	10.2×	1e-03
negative regulation of protein ubiquitination	5	10.1×	8e-03

Disease & clinical

Clinical variants and AI predictions

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

745 predictions. Top by Δscore:

Variant	Effect	Δscore
7:44796789:TTGAG:T	donor_loss	1.0000
7:44796790:TGAG:T	donor_loss	1.0000
7:44796791:GAGGT:G	donor_loss	1.0000
7:44796792:AGG:A	donor_loss	1.0000
7:44796793:GG:G	donor_loss	1.0000
7:44799245:A:AG	acceptor_gain	1.0000
7:44799246:G:GG	acceptor_gain	1.0000
7:44799246:GCT:G	acceptor_gain	1.0000
7:44799390:A:AG	acceptor_gain	1.0000
7:44799391:G:GG	acceptor_gain	1.0000
7:44799693:T:G	acceptor_gain	1.0000
7:44799696:TGACA:T	acceptor_loss	1.0000
7:44799697:GACA:G	acceptor_loss	1.0000
7:44799699:CAGGG:C	acceptor_loss	1.0000
7:44799700:A:AG	acceptor_gain	1.0000
7:44799700:AG:A	acceptor_gain	1.0000
7:44799700:AGG:A	acceptor_gain	1.0000
7:44799700:AGGG:A	acceptor_loss	1.0000
7:44799700:AGGGT:A	acceptor_gain	1.0000
7:44799701:G:GT	acceptor_gain	1.0000
7:44799701:GG:G	acceptor_gain	1.0000
7:44799701:GGG:G	acceptor_gain	1.0000
7:44799701:GGGT:G	acceptor_gain	1.0000
7:44799701:GGGTG:G	acceptor_gain	1.0000
7:44799840:TCCC:T	donor_gain	1.0000
7:44799870:GAGTG:G	donor_gain	1.0000
7:44799872:GTG:G	donor_gain	1.0000
7:44799875:G:GG	donor_gain	1.0000
7:44801283:CAAG:C	acceptor_loss	1.0000
7:44801284:A:AG	acceptor_gain	1.0000

AlphaMissense

1108 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:44799469:T:C	F60L	0.999
7:44799471:T:A	F60L	0.999
7:44799471:T:G	F60L	0.999
7:44799708:G:C	D66H	0.999
7:44799709:A:T	D66V	0.999
7:44799846:T:C	F112L	0.999
7:44799848:T:A	F112L	0.999
7:44799848:T:G	F112L	0.999
7:44801289:T:C	L122S	0.999
7:44799396:T:A	N35K	0.998
7:44799396:T:G	N35K	0.998
7:44799451:C:G	H54D	0.998
7:44799455:G:C	R55T	0.998
7:44799456:A:C	R55S	0.998
7:44799456:A:T	R55S	0.998
7:44799470:T:C	F60S	0.998
7:44799706:G:T	G65V	0.998
7:44799710:C:A	D66E	0.998
7:44799710:C:G	D66E	0.998
7:44799727:G:A	G72D	0.998
7:44799727:G:T	G72V	0.998
7:44799759:T:C	F83L	0.998
7:44799761:T:A	F83L	0.998
7:44799761:T:G	F83L	0.998
7:44799765:G:C	D85H	0.998
7:44799805:T:C	L98S	0.998
7:44799836:T:A	N108K	0.998
7:44799836:T:G	N108K	0.998
7:44799849:T:C	F113L	0.998
7:44799851:C:A	F113L	0.998

dbSNP variants (sampled 300 via entrez): RS1000118396 (7:44794786 C>T), RS1000249398 (7:44802504 T>G), RS1000292328 (7:44799505 T>C), RS1000444121 (7:44797562 T>C), RS1000628094 (7:44797306 G>A,T), RS1000753663 (7:44803201 CTTTT>C,CT,CTT,CTTT,CTTTTT), RS1001285237 (7:44797217 C>A,G,T), RS1001568402 (7:44801879 C>T), RS1002135534 (7:44797024 G>C,T), RS1002396865 (7:44802364 G>A), RS1002548829 (7:44796462 C>T), RS1002690286 (7:44798381 C>T), RS1002951129 (7:44796445 C>A), RS1003240232 (7:44800934 C>T), RS1003353480 (7:44796223 G>A)

Disease associations

OMIM: gene MIM:123840 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
amyotrophic lateral sclerosis	Limited	Autosomal dominant

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

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90002396_385	Mean reticulocyte volume	3.000000e-73
GCST90002403_571	Red blood cell count	7.000000e-37

EFO canonical traits (2, from GWAS)

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

MeSH disease descriptors (1)

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)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 194,194 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL160	CYCLOSPORINE	4	168,247
CHEMBL480	LANSOPRAZOLE	4	24,317
CHEMBL1651956	ALISPORIVIR	3	822
CHEMBL1269597	SCY 635	2	557
CHEMBL1688529	NIM811	2	164
CHEMBL2107422	GECLOSPORIN	2	87

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

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)

279 measured of 312 human assays (313 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
[(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
(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	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
(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
(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	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
(3S,6S,9S,12R,15S,18S,21S,24S,27R,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-24-[(1S)-1-methoxy-2-pyrrolidin-1-ylethyl]-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

271 with measured affinity, of 657 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,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	496160: Inhibition of calcineurin phosphatase activity of CyPA	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	581778: Inhibition of human recombinant cyclophilin-associted cis-trans propyl isomerase activity	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-(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
(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
methyl 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-carboxylate	770489: Inhibition of CypA PPIase activity (unknown origin) using Glt-(Ala)n-Pro-Phe-4-nitroanilides as substrate	ki	0.0118	uM
5-[[4-[(E,4R,5R)-5-[(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]-5-hydroxy-4-methylpent-1-enyl]phenyl]methylcarbamoyl]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid	580954: Inhibition of cyclosporin binding to Cyp18 by fluorescence polarization competition assay	kd	0.0120	uM
(2R,5S,11S,14S,18E)-2,11-dimethyl-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	0.0120	uM
N-(9H-fluoren-9-ylcarbamoyl)-2-phenylmethoxybenzamide	427507: Inhibition of peptidyl-prolyl isomerase activity of Cyclophilin A	ic50	0.0121	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases methylation, affects cotreatment	4
sodium arsenite	decreases expression, increases expression	3
Cisplatin	affects binding, decreases response to substance, increases expression	3
Copper	decreases expression, affects binding	3
Tobacco Smoke Pollution	affects expression, increases expression, increases metabolic processing	3
Cyclosporine	decreases expression, increases expression	3
torcetrapib	increases expression	2
Arsenic Trioxide	increases expression	2
Quercetin	increases expression	2
Valproic Acid	decreases expression, affects 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	affects cotreatment, affects localization, decreases expression	1
trichostatin A	affects cotreatment, decreases expression	1
ferric ammonium citrate	increases expression, decreases reaction	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

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1H23	PPIA-/- Jurkat	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00542412	PHASE4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00560287	PHASE4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00613899	PHASE4	COMPLETED	Feasibility of Telesurveillance and Home Cough Assistance for Amyotrophic Lateral Patients (ALS)
NCT04997954	PHASE4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT06849115	PHASE4	COMPLETED	Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations
NCT07223723	PHASE4	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	PHASE3	COMPLETED	Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
NCT00035815	PHASE3	COMPLETED	Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
NCT00047723	PHASE3	COMPLETED	Minocycline to Treat Amyotrophic Lateral Sclerosis
NCT00069186	PHASE3	UNKNOWN	Study of Creatine Monohydrate in Patients With Amyotrophic Lateral Sclerosis
NCT00136110	PHASE3	COMPLETED	Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis
NCT00330681	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS)
NCT00349622	PHASE3	COMPLETED	Clinical Trial Ceftriaxone in Subjects With ALS
NCT00372879	PHASE3	COMPLETED	Clinical Trial of Vitamin E to Treat Muscular Cramps in Patients With ALS
NCT00415519	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS) Who Met Severity Classification III
NCT00424463	PHASE3	COMPLETED	Expanded Controlled Study of Safety and Efficacy of MCI-186 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00868166	PHASE3	COMPLETED	Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS
NCT00965497	PHASE3	COMPLETED	Escitalopram (Lexapro) for Depression MS or ALS
NCT01016522	PHASE3	TERMINATED	Safety and Tolerability of the Ketogenic Diet in Amyotrophic Lateral Sclerosis (ALS)
NCT01160263	PHASE3	COMPLETED	Study of Dopamine and Serotonin Transporters in Patients With Amyotrophic Lateral Sclerosis and Controls
NCT01281189	PHASE3	COMPLETED	Phase 3 Study of Dexpramipexole in ALS
NCT01492686	PHASE3	COMPLETED	Phase 3 Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis
NCT01583088	PHASE3	TERMINATED	Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation
NCT01622088	PHASE3	TERMINATED	Phase 3 Extension Study of Dexpramipexole in ALS
NCT02496767	PHASE3	COMPLETED	Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year
NCT02623699	PHASE3	COMPLETED	An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)
NCT02936635	PHASE3	COMPLETED	A Study for Patients Who Completed VITALITY-ALS (CY 4031)
NCT03127267	PHASE3	RECRUITING	Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
NCT03280056	PHASE3	COMPLETED	Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients
NCT03491462	PHASE3	COMPLETED	Arimoclomol in Amyotropic Lateral Sclerosis
NCT03505021	PHASE3	COMPLETED	Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS
NCT03548311	PHASE3	COMPLETED	Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
NCT03690791	PHASE3	UNKNOWN	Efficacy of Cannabinoids in Amyotrophic Lateral Sclerosis or Motor Neurone Disease
NCT03800524	PHASE3	UNKNOWN	Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS
NCT03836716	PHASE3	TERMINATED	Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
NCT03948178	PHASE3	TERMINATED	Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
NCT04165824	PHASE3	COMPLETED	Safety Study of Oral Edaravone Administered in Subjects With ALS
NCT04248465	PHASE3	TERMINATED	An Efficacy and Safety Study of Ravulizumab in ALS Participants
NCT04569084	PHASE3	TERMINATED	Efficacy and Safety Study of Oral Edaravone Administered in Subjects With ALS