PPIF

Summary

PPIF (peptidylprolyl isomerase F, HGNC:9259) is a protein-coding gene on chromosome 10q22.3, encoding Peptidyl-prolyl cis-trans isomerase F, mitochondrial (P30405). PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding.

The protein encoded by this gene is 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. This protein is part of the mitochondrial permeability transition pore in the inner mitochondrial membrane. Activation of this pore is thought to be involved in the induction of apoptotic and necrotic cell death.

Source: NCBI Gene 10105 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 27 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005729

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9259
Approved symbol	PPIF
Name	peptidylprolyl isomerase F
Location	10q22.3
Locus type	gene with protein product
Status	Approved
Aliases	hCyP3, Cyp-D, CypD
Ensembl gene	ENSG00000108179
Ensembl biotype	protein_coding
OMIM	604486
Entrez	10105

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000225174, ENST00000448165, ENST00000472580, ENST00000492149, ENST00000498681, ENST00000871351, ENST00000955650, ENST00000955651

RefSeq mRNA: 1 — MANE Select: NM_005729 NM_005729

CCDS: CCDS7358

Canonical transcript exons

ENST00000225174 — 6 exons

Exon	Start	End
ENSE00000429803	79351487	79351583
ENSE00001136191	79353707	79355334
ENSE00003503708	79347469	79347743
ENSE00003506032	79349665	79349753
ENSE00003587434	79352317	79352392
ENSE00003637288	79349076	79349106

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.95.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 140.5877 / max 3148.6965, expressed in 1825 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
105788	117.8740	1822
105790	11.3732	1787
105789	10.9330	1794
105792	0.4075	165

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
amniotic fluid	UBERON:0000173	98.95	gold quality
right adrenal gland cortex	UBERON:0035827	98.93	gold quality
right adrenal gland	UBERON:0001233	98.88	gold quality
left adrenal gland	UBERON:0001234	98.85	gold quality
adrenal cortex	UBERON:0001235	98.69	gold quality
left adrenal gland cortex	UBERON:0035825	98.68	gold quality
adrenal gland	UBERON:0002369	98.52	gold quality
adrenal tissue	UBERON:0018303	98.44	gold quality
periodontal ligament	UBERON:0008266	97.79	gold quality
body of tongue	UBERON:0011876	97.31	gold quality
right lobe of liver	UBERON:0001114	97.20	gold quality
apex of heart	UBERON:0002098	97.03	gold quality
heart left ventricle	UBERON:0002084	96.81	gold quality
cardiac ventricle	UBERON:0002082	96.75	gold quality
left ventricle myocardium	UBERON:0006566	96.67	gold quality
right atrium auricular region	UBERON:0006631	96.36	gold quality
monocyte	CL:0000576	96.29	gold quality
cardiac atrium	UBERON:0002081	96.29	gold quality
pharyngeal mucosa	UBERON:0000355	96.21	gold quality
liver	UBERON:0002107	96.02	gold quality
body of pancreas	UBERON:0001150	95.96	gold quality
tongue	UBERON:0001723	95.96	gold quality
mononuclear cell	CL:0000842	95.93	gold quality
mucosa of transverse colon	UBERON:0004991	95.93	gold quality
leukocyte	CL:0000738	95.62	gold quality
skin of leg	UBERON:0001511	95.62	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.58	gold quality
tongue squamous epithelium	UBERON:0006919	95.52	gold quality
spinal cord	UBERON:0002240	95.43	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.43	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	34.85
E-CURD-112	yes	31.86
E-HCAD-6	yes	18.92
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

70 targeting PPIF, 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-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-10394-5P	99.65	66.83	1852

Literature-anchored findings (GeneRIF, showing 31)

• Cyclophilin D protects cell from cell death. (PMID:12077116)
• Crystal structure of human cyclophilin D in complex with its inhibitor, cyclosporin A at 0.96-A resolution, using a K133I mutant of human CypD (PMID:18076075)
• There was increased Ca(2+), Ca(2+), mCICR, MPTP opening, and expression of cyclophilin D and decreased DeltaPsim in POAG TM cells compared with control cells. (PMID:18614807)
• Cyclophilin D may play a role as a redox sensor in mitochondria of mammalian cells transmitting information on the redox environment to target proteins. (PMID:19735641)
• Data show that show that the molecular chaperone heat shock protein 60 (Hsp60) directly associates with cyclophilin D (CypD). (PMID:20978188)
• adult viable human brain and liver mitochondria possess an active CypD-sensitive mitochondrial permeability transition (PMID:21121808)
• Human coronavirus-induced neuronal programmed cell death required cyclophilin d but not caspase 3 caspase 9 activities. (PMID:22013052)
• These results suggest Cyp-D’s critical role in UVB/oxidative stress-induced skin cell death. (PMID:22892127)
• CypD directs mitochondria-to-nuclei inflammatory gene expression in normal and tumor cells (PMID:23303179)
• cisplatin-induced non-apoptotic death requires mitochondria Cyp-D-p53 signaling in pancreatic cancer cells (PMID:23845906)
• The p53/Cyp-D mitochondrial complexation was prevented by CsA or Cyp-D silencing. (PMID:24343341)
• In summary, the results of the present study provide mechanistic evidence that both apoptosis and programmed necrosis attribute to berberine’s cytotoxicity in prostate cancer cells. (PMID:24946211)
• molecular determinants necessary for Cyclophilin D activity regulation and binding to proposed pore constituents thereby regulating the mitochondrial permeability transition pore. (PMID:25445707)
• Cyp-D silencing down-regulated mitochondrial transcripts initiated from the heavy strand promoter 2 [i.e., NADH dehydrogenase 1 (ND1) by 11-fold; cytochrome oxidase 1 (COX1) by 4-fold; and ATP synthase subunit 6 (ATP6) by 6.5-fold. (PMID:25837584)
• Results show that CypD interacts with SPG7 and VDAC to form the mitochondrial permeability transition pore complex (PTP)and its CsA-binding region is necessary for PTP formation. (PMID:26387735)
• The influx of unfolded p53 into the mitochondrial matrix in response to oxidative stress indirectly activates the normally inhibited CypD by displacing it from Trap1 complexes. This activates CypD’s isomerase activity. Liberated CypD then isomerizes multiple proteins including p53 (causing p53 aggregation) and the structural components of the mPTP pore, inducing pore opening. (PMID:27515399)
• cyclophilin D may modify mitochondrial features by inducing the translocation of molecules to the mitochondria through the mechanism associated with cellular energy metabolism (PMID:27864141)
• CyPD regulates mitochondrial metabolism, and likely cell survival, by promoting more efficient electrons flow through the respiratory chain via increased supercomplex formation (PMID:27916505)
• The present study is to investigate the role of CypD in regulating the mitochondrial dynamics relevant to oxidative stress induced neuron dysfunctions. (PMID:27993675)
• Binding of signal transducer and activator of transcription 3 (STAT3) to cyclophilin D (CypD) was important for reducing mitochondrial reactive oxygen species (ROS) production after oxidative stress. (PMID:28351946)
• This review discusses previous studies to provide comprehensive information on the physiological role of cyclophilin D as well as PTP opening in the cell that can be taken into consideration for the development of new PTP inhibitors. [review] (PMID:28378042)
• the important yet enigmatic nature of CyPD (PPIF) somehow makes it a master regulator, yet a troublemaker, for mitochondrial function. (PMID:30558250)
• Targeting cyclophilin-D by miR-1281 protects human macrophages from Mycobacterium tuberculosis-induced programmed necrosis and apoptosis. (PMID:31884421)
• microRNA-1203 targets and silences cyclophilin D to protect human endometrial cells from oxygen and glucose deprivation-re-oxygenation. (PMID:32041924)
• RNase T1 Refolding Assay for Determining Mitochondrial Cyclophilin D Activity: A Novel In Vitro Method Applicable in Drug Research and Discovery. (PMID:32275395)
• Overexpression of TICRR and PPIF confer poor prognosis in endometrial cancer identified by gene co-expression network analysis. (PMID:33495413)
• Formation of High-Conductive C Subunit Channels upon Interaction with Cyclophilin D. (PMID:34681682)
• Cinnamtannin B-1 Inhibits the Progression of Osteosarcoma by Regulating the miR-1281/PPIF Axis. (PMID:36273900)
• Role of the mitochondrial protein cyclophilin D in skin wound healing and collagen secretion. (PMID:38564292)
• Mitochondrial CypD Acetylation Promotes Endothelial Dysfunction and Hypertension. (PMID:38639088)
• Dissecting prostate Cancer: Single-Cell insight into Macrophage Diversity, molecular Prognosticators, and the role of Peptidylprolyl Isomerase F. (PMID:38959543)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppifb	ENSDARG00000052842
mus_musculus	Ppif	ENSMUSG00000021868
rattus_norvegicus	Ppif	ENSRNOG00000010558
drosophila_melanogaster	CG7768	FBGN0036415

Paralogs (22): PPIE (ENSG00000084072), PPIL2 (ENSG00000100023), PPWD1 (ENSG00000113593), NKTR (ENSG00000114857), PPIL4 (ENSG00000131013), PPIL1 (ENSG00000137168), PPIG (ENSG00000138398), CWC27 (ENSG00000153015), PPIB (ENSG00000166794), PPIC (ENSG00000168938), PPID (ENSG00000171497), PPIH (ENSG00000171960), PPIL6 (ENSG00000185250), PPIA (ENSG00000196262), PPIAL4G (ENSG00000236334), PPIL3 (ENSG00000240344), PPIAL4A (ENSG00000263353), PPIAL4H (ENSG00000270339), PPIAL4E (ENSG00000271567), PPIAL4F (ENSG00000279782), PPIAL4C (ENSG00000288867), PPIAL4D (ENSG00000289549)

Protein

Protein identifiers

Peptidyl-prolyl cis-trans isomerase F, mitochondrial — P30405 (reviewed: P30405)

Alternative names: Cyclophilin D, Cyclophilin F, Mitochondrial cyclophilin, Rotamase F

All UniProt accessions (3): P30405, H0Y548, R4GN99

UniProt curated annotations — full annotation on UniProt →

Function. PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding. Involved in regulation of the mitochondrial permeability transition pore (mPTP). It is proposed that its association with the mPTP is masking a binding site for inhibiting inorganic phosphate (Pi) and promotes the open probability of the mPTP leading to apoptosis or necrosis; the requirement of the PPIase activity for this function is debated. In cooperation with mitochondrial p53/TP53 is involved in activating oxidative stress-induced necrosis. Involved in modulation of mitochondrial membrane F(1)F(0) ATP synthase activity and regulation of mitochondrial matrix adenine nucleotide levels. Has anti-apoptotic activity independently of mPTP and in cooperation with BCL2 inhibits cytochrome c-dependent apoptosis.

Subunit / interactions. Associates with the mitochondrial membrane ATP synthase F(1)F(0) ATP synthase; the association is increased by inorganic phosphate (Pi) and decreased by cyclosporin A (CsA). Interacts with ATP5F1B; ATP5PD and ATP5PO. Interacts with SLC25A3; the interaction is impaired by CsA. Interacts with BCL2; the interaction is impaired by CsA. Interacts with TP53; the association implicates preferentially tetrameric TP53, is induced by oxidative stress and is impaired by CsA. Interacts with C1QBP. Interacts with MCUR1. Component of the mitochondrial permeability transition pore complex (mPTPC), at least composed of SPG7, VDAC1 and PPIF. Interacts with SPG7.

Subcellular location. Mitochondrion matrix.

Post-translational modifications. Acetylated at Lys-167; deacetylated at Lys-167 by SIRT3. Benzoylated at Lys-73 and Lys-197. Debenzoylated by SIRT3; inhibiting its cooperation with p53/TP53.

Activity regulation. Inhibited by cyclosporin A (CsA). Is displaced by CsA from the mPTP leading to a lower open probability of the mPTP.

Similarity. Belongs to the cyclophilin-type PPIase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P30405-1	1	yes
P30405-2	2

RefSeq proteins (1): NP_005720* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002130	Cyclophilin-type_PPIase_dom	Domain
IPR020892	Cyclophilin-type_PPIase_CS	Conserved_site
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 (36 total): strand 12, modified residue 9, turn 5, mutagenesis site 3, helix 3, transit peptide 1, chain 1, splice variant 1, domain 1

Structure

Experimental structures (PDB)

73 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7R2H	X-RAY DIFFRACTION	0.79
4O8H	X-RAY DIFFRACTION	0.85
2Z6W	X-RAY DIFFRACTION	0.96
3RCG	X-RAY DIFFRACTION	0.97
7TH6	X-RAY DIFFRACTION	0.97
7PMT	X-RAY DIFFRACTION	0.98
4J5E	X-RAY DIFFRACTION	0.99
7OGI	X-RAY DIFFRACTION	1.01
4J5C	X-RAY DIFFRACTION	1.03
3R4G	X-RAY DIFFRACTION	1.05
7TGT	X-RAY DIFFRACTION	1.06
3RDA	X-RAY DIFFRACTION	1.07
3R59	X-RAY DIFFRACTION	1.1
7R2L	X-RAY DIFFRACTION	1.1
7THF	X-RAY DIFFRACTION	1.1
3RCF	X-RAY DIFFRACTION	1.15
7THD	X-RAY DIFFRACTION	1.16
7TGU	X-RAY DIFFRACTION	1.21
5A0E	X-RAY DIFFRACTION	1.25
9RLM	X-RAY DIFFRACTION	1.25
3RCK	X-RAY DIFFRACTION	1.26
6R9U	X-RAY DIFFRACTION	1.26
7R2J	X-RAY DIFFRACTION	1.26
4J58	X-RAY DIFFRACTION	1.28
7TH7	X-RAY DIFFRACTION	1.3
7R2I	X-RAY DIFFRACTION	1.31
4J5D	X-RAY DIFFRACTION	1.32
3R54	X-RAY DIFFRACTION	1.35
6R8O	X-RAY DIFFRACTION	1.36
3R56	X-RAY DIFFRACTION	1.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30405-F1	88.87	0.80

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 (9): 197, 203, 67, 67, 73, 86, 167, 175, 190

Mutagenesis-validated functional residues (3):

Position	Phenotype
73	abolished debenzoylation by sirt3; when associated with a-197.
197	abolished debenzoylation by sirt3; when associated with a-73.
203	blocks ca(2+)-induced mptp opening and reduces hydrogen peroxide-induced cell death.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 366 (showing top): ELVIDGE_HYPOXIA_DN, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GRUETZMANN_PANCREATIC_CANCER_DN, ENK_UV_RESPONSE_KERATINOCYTE_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_MITOCHONDRIAL_TRANSPORT, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_RESPONSE_TO_METAL_ION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (23): response to ischemia (GO:0002931), protein folding (GO:0006457), apoptotic mitochondrial changes (GO:0008637), obsolete regulation of proton-transporting ATPase activity, rotational mechanism (GO:0010849), negative regulation of apoptotic process (GO:0043066), regulation of mitochondrial membrane permeability (GO:0046902), mitochondrial depolarization (GO:0051882), necroptotic process (GO:0070266), cellular response to hydrogen peroxide (GO:0070301), cellular response to arsenic-containing substance (GO:0071243), cellular response to calcium ion (GO:0071277), negative regulation of release of cytochrome c from mitochondria (GO:0090201), negative regulation of oxidative phosphorylation (GO:0090324), skeletal muscle fiber differentiation (GO:0098528), regulation of mitochondrial membrane permeability involved in programmed necrotic cell death (GO:1902445), mitochondrial outer membrane permeabilization involved in programmed cell death (GO:1902686), negative regulation of intrinsic apoptotic signaling pathway (GO:2001243), protein peptidyl-prolyl isomerization (GO:0000413), apoptotic process (GO:0006915), response to oxidative stress (GO:0006979), mitochondrion organization (GO:0007005), programmed cell death (GO:0012501), muscle structure development (GO:0061061)

GO Molecular Function (4): peptidyl-prolyl cis-trans isomerase activity (GO:0003755), cyclosporin A binding (GO:0016018), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (5): cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial permeability transition pore complex (GO:0005757), mitochondrial matrix (GO:0005759), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to stress	2
apoptotic process	2
mitochondrion	2
programmed necrotic cell death	2
negative regulation of apoptotic signaling pathway	2
programmed cell death	2
binding	2
cellular anatomical structure	2
cellular process	1
protein maturation	1
mitochondrion organization	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
regulation of membrane permeability	1
regulation of mitochondrial membrane potential	1
membrane depolarization	1
cellular response to reactive oxygen species	1
response to hydrogen peroxide	1
response to arsenic-containing substance	1
cellular response to chemical stimulus	1
response to calcium ion	1
cellular response to metal ion	1
release of cytochrome c from mitochondria	1
negative regulation of organelle organization	1
regulation of release of cytochrome c from mitochondria	1
regulation of oxidative phosphorylation	1
oxidative phosphorylation	1
negative regulation of cellular respiration	1
myotube differentiation	1
skeletal muscle cell differentiation	1
regulation of mitochondrial membrane permeability	1
positive regulation of mitochondrial membrane permeability	1
intrinsic apoptotic signaling pathway	1
negative regulation of intracellular signal transduction	1
regulation of intrinsic apoptotic signaling pathway	1
peptidyl-proline modification	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cis-trans isomerase activity	1
catalytic activity, acting on a protein	1

Protein interactions and networks

STRING

3518 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPIF	VDAC1	P21796	995
PPIF	TP53	P04637	990
PPIF	ATP5PO	P48047	989
PPIF	HSP90AA1	P07900	978
PPIF	HSP90AB1	P08238	978
PPIF	SLC25A4	P12235	977
PPIF	ITPR1	Q14643	960
PPIF	SPG7	Q9UQ90	931
PPIF	HSPA9	P30036	925
PPIF	ITPR3	Q14573	905
PPIF	BCL2	P10415	832
PPIF	CYCS	P00001	828
PPIF	TSPO	P30536	804
PPIF	GSK3B	P49841	788
PPIF	CYP27B1	O15528	787

IntAct

88 interactions, top by confidence:

A	B	Type	Score
ABI2	PPIF	psi-mi:“MI:0915”(physical association)	0.670
PPIF	ABI2	psi-mi:“MI:0915”(physical association)	0.670
ETFRF1	NDUFAB1	psi-mi:“MI:0914”(association)	0.640
PPIF	TP53	psi-mi:“MI:0915”(physical association)	0.640
TP53	PPIF	psi-mi:“MI:0915”(physical association)	0.640
TP53	PPIF	psi-mi:“MI:0407”(direct interaction)	0.640
PPIF	BANP	psi-mi:“MI:0915”(physical association)	0.560
PPIF	CMTM5	psi-mi:“MI:0915”(physical association)	0.560
PPIF	MAGEA11	psi-mi:“MI:0915”(physical association)	0.560
PPIF	ABI2	psi-mi:“MI:0915”(physical association)	0.560
YIF1A	PPIF	psi-mi:“MI:0915”(physical association)	0.560
PPIF	ARFIP2	psi-mi:“MI:0915”(physical association)	0.560
SYP	PPIF	psi-mi:“MI:0915”(physical association)	0.560
PPIF	CIDEB	psi-mi:“MI:0915”(physical association)	0.560
PPIF	PRB3	psi-mi:“MI:0915”(physical association)	0.560
FAM25C	PPIF	psi-mi:“MI:0915”(physical association)	0.560
MUC1	PPIF	psi-mi:“MI:0915”(physical association)	0.560
PPIF	AGTRAP	psi-mi:“MI:0915”(physical association)	0.560
PPIF	FKBP7	psi-mi:“MI:0915”(physical association)	0.560
PPIF	SYPL1	psi-mi:“MI:0915”(physical association)	0.560
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
PPIF	APP	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (179): ABI2 (Two-hybrid), BANP (Two-hybrid), CMTM5 (Two-hybrid), GSTK1 (Co-fractionation), PPIF (Co-fractionation), PPIF (Co-fractionation), PPIF (Co-fractionation), PPIF (Co-fractionation), PPIF (Co-fractionation), PPIF (Co-fractionation), S100A10 (Co-fractionation), TANGO2 (Co-fractionation), TBL1XR1 (Co-fractionation), BANP (Two-hybrid), PPIF (Two-hybrid)

ESM2 similar proteins: A4FV72, B3A0R0, D4AY02, O49605, O93826, O94273, P0C1H9, P0C1I0, P0C1I1, P0CP78, P0CP79, P23284, P23285, P24367, P24368, P24369, P30405, P30412, P35176, P45877, P52009, P52013, P52014, P80311, P84343, Q01490, Q08752, Q08E11, Q27774, Q2UGK2, Q4I5R9, Q4IPH4, Q4WP12, Q5B4E7, Q5B4R3, Q5R723, Q6C4W6, Q6CBP4, Q6DGG0, Q7S7Z6

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

3 interactions.

A	Effect	B	Mechanism
GSK3B	“up-regulates activity”	PPIF	phosphorylation
PPIF	“up-regulates activity”	ATP5PO	binding
AKT2	“up-regulates activity”	PPIF	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 60 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
VEGFR2 mediated cell proliferation	6	83.6×	1e-08
Innate Immune System	7	4.3×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
Ras protein signal transduction	5	18.7×	2e-03
positive regulation of apoptotic process	7	7.2×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

980 predictions. Top by Δscore:

Variant	Effect	Δscore
10:79347740:GGAG:G	donor_gain	1.0000
10:79347741:G:GT	donor_gain	1.0000
10:79347741:GAG:G	donor_gain	1.0000
10:79347744:G:GG	donor_gain	1.0000
10:79349074:A:AG	acceptor_gain	1.0000
10:79349075:G:GG	acceptor_gain	1.0000
10:79349103:GCTG:G	donor_gain	1.0000
10:79349655:C:A	acceptor_gain	1.0000
10:79349661:TCA:T	acceptor_loss	1.0000
10:79349662:CA:C	acceptor_loss	1.0000
10:79349663:A:AG	acceptor_gain	1.0000
10:79349664:G:GC	acceptor_gain	1.0000
10:79349664:G:GT	acceptor_loss	1.0000
10:79349664:GA:G	acceptor_gain	1.0000
10:79349664:GAGA:G	acceptor_gain	1.0000
10:79349664:GAGAA:G	acceptor_gain	1.0000
10:79349755:T:A	donor_loss	1.0000
10:79351484:CAGG:C	acceptor_loss	1.0000
10:79351485:A:AC	acceptor_loss	1.0000
10:79351485:A:AG	acceptor_gain	1.0000
10:79351485:AG:A	acceptor_gain	1.0000
10:79351485:AGGC:A	acceptor_gain	1.0000
10:79351485:AGGCG:A	acceptor_gain	1.0000
10:79351486:G:GA	acceptor_gain	1.0000
10:79351486:GG:G	acceptor_gain	1.0000
10:79351486:GGC:G	acceptor_gain	1.0000
10:79351486:GGCG:G	acceptor_gain	1.0000
10:79351486:GGCGG:G	acceptor_gain	1.0000
10:79351585:T:A	donor_loss	1.0000
10:79352312:TGCAG:T	acceptor_loss	1.0000

AlphaMissense

1354 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:79349742:T:C	F102L	0.999
10:79349744:C:A	F102L	0.999
10:79349744:C:G	F102L	0.999
10:79352375:C:G	C157W	0.999
10:79349669:C:A	N77K	0.998
10:79349669:C:G	N77K	0.998
10:79349724:C:G	H96D	0.998
10:79349728:G:T	R97M	0.998
10:79351493:G:C	D108H	0.998
10:79351494:A:C	D108A	0.998
10:79351494:A:T	D108V	0.998
10:79351495:C:A	D108E	0.998
10:79351495:C:G	D108E	0.998
10:79351512:G:A	G114D	0.998
10:79351512:G:T	G114V	0.998
10:79351544:T:C	F125L	0.998
10:79351545:T:C	F125S	0.998
10:79351546:T:A	F125L	0.998
10:79351546:T:G	F125L	0.998
10:79352354:C:A	N150K	0.998
10:79352354:C:G	N150K	0.998
10:79352363:G:C	Q153H	0.998
10:79352363:G:T	Q153H	0.998
10:79352367:T:C	F155L	0.998
10:79352369:C:A	F155L	0.998
10:79352369:C:G	F155L	0.998
10:79353709:T:C	L164S	0.998
10:79349684:C:G	C82W	0.997
10:79349728:G:C	R97T	0.997
10:79349729:G:C	R97S	0.997

dbSNP variants (sampled 300 via entrez): RS1000075639 (10:79348807 G>T), RS1000269118 (10:79355250 T>A), RS1000576438 (10:79355553 G>A), RS1000613949 (10:79353900 C>A,T), RS1000623957 (10:79353535 G>A), RS1000781538 (10:79349462 A>G), RS1001248070 (10:79352800 C>T), RS1001443717 (10:79347165 C>T), RS1002234615 (10:79348012 C>G), RS1002250475 (10:79354216 T>C), RS1002304546 (10:79354451 T>G), RS1002419681 (10:79350162 A>G), RS1002463374 (10:79348615 C>T), RS1002974807 (10:79352759 A>G), RS1003088929 (10:79353122 G>A)

Disease associations

OMIM: gene MIM:604486 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000817_161	Height	4.000000e-13
GCST000817_5	Height	6.000000e-10
GCST004611_174	High light scatter reticulocyte count	4.000000e-11
GCST004612_111	High light scatter reticulocyte percentage of red cells	6.000000e-11
GCST006585_871	Blood protein levels	2.000000e-06
GCST008839_474	Height	4.000000e-18
GCST009391_1283	Metabolite levels	6.000000e-06
GCST009391_1390	Metabolite levels	6.000000e-06
GCST010244_180	Triglyceride levels	2.000000e-08
GCST012227_612	Hip circumference adjusted for BMI	4.000000e-08
GCST012227_613	Hip circumference adjusted for BMI	1.000000e-08
GCST90000025_444	Appendicular lean mass	5.000000e-19
GCST90002385_485	High light scatter reticulocyte count	2.000000e-19
GCST90002386_406	High light scatter reticulocyte percentage of red cells	6.000000e-18
GCST90002387_362	Immature fraction of reticulocytes	4.000000e-14
GCST90002395_26	Mean platelet volume	2.000000e-09
GCST90013406_84	Liver enzyme levels (alkaline phosphatase)	6.000000e-14
GCST90020028_86	Hip circumference adjusted for BMI	2.000000e-10
GCST90020028_87	Hip circumference adjusted for BMI	2.000000e-17

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0009792	valine measurement
EFO:0010368	lysophosphatidylethanolamine 18:1 measurement
EFO:0004530	triglyceride measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3325306 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 169,790 (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
CHEMBL1651956	ALISPORIVIR	3	822
CHEMBL1269597	SCY 635	2	557
CHEMBL1688529	NIM811	2	164

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

Binding affinities (BindingDB)

183 measured of 185 human assays (185 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
[(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
(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-[4-(2-methoxyethyl)piperazin-1-yl]ethyl]-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

38 potent at pChembl≥5 of 42 total, top 38 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.05	Kd	0.9	nM	CHEMBL3344501
9.00	Kd	1	nM	ALISPORIVIR
8.52	Ki	3	nM	CHEMBL6078181
8.51	Kd	3.1	nM	SCY 635
8.38	Kd	4.2	nM	NIM811
8.30	Ki	5	nM	CYCLOSPORINE
8.30	Ki	5	nM	CHEMBL6108990
8.10	Kd	8	nM	CHEMBL6162052
7.85	Kd	14	nM	CYCLOSPORINE
7.70	IC50	20	nM	CYCLOSPORINE
7.70	Ki	20	nM	CHEMBL6120896
7.24	Ki	57	nM	CHEMBL6078272
7.12	Ki	75	nM	CHEMBL6078337
7.10	Kd	80	nM	CHEMBL6148976
7.10	Kd	80	nM	CHEMBL6142884
6.75	Kd	180	nM	CHEMBL6145925
6.70	Kd	200	nM	CYCLOSPORINE
6.61	EC50	244	nM	CHEMBL6162052
6.50	Ki	320	nM	CHEMBL6078060
6.44	Kd	360	nM	CHEMBL6167950
6.40	Kd	400	nM	CHEMBL6132693
6.33	EC50	463	nM	CYCLOSPORINE
6.24	Kd	580	nM	CHEMBL6161717
6.21	Kd	610	nM	CHEMBL6103162
6.00	Kd	1010	nM	CHEMBL6149779
5.92	Kd	1200	nM	CHEMBL6134476
5.85	Kd	1410	nM	CHEMBL4290606
5.83	Ki	1470	nM	CHEMBL6074436
5.82	Kd	1500	nM	CHEMBL6134728
5.77	Kd	1710	nM	CHEMBL4169345
5.64	IC50	2300	nM	CHEMBL6103162
5.62	Kd	2400	nM	CHEMBL6143270
5.53	Kd	2970	nM	CHEMBL6148626
5.31	IC50	4910	nM	CHEMBL203193
5.23	Kd	5850	nM	CHEMBL6146402
5.20	Kd	6300	nM	CHEMBL6160116
5.13	IC50	7380	nM	CHEMBL4169345
5.04	Kd	9100	nM	CHEMBL6165058

PubChem BioAssay actives

5 with measured affinity, of 7 total; 5 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)-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	1168836: Binding affinity to human cyclophilin F by surface plasmon resonance method	kd	0.0009	uM
(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	1168836: Binding affinity to human cyclophilin F by surface plasmon resonance method	kd	0.0010	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	1168836: Binding affinity to human cyclophilin F by surface plasmon resonance method	kd	0.0031	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	1168836: Binding affinity to human cyclophilin F by surface plasmon resonance method	kd	0.0042	uM
(3S,6S,9S,12S,15S,18S,21S,24S,27R,30S,33S)-12-ethyl-15-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,7,9,10,16,19,22,25,27,30-decamethyl-4-(3-methylbut-2-enyl)-6,21,24,33-tetrakis(2-methylpropyl)-3,18-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	1178330: Binding affinity to cyclophilin D (unknown origin)	kd	0.0600	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, increases methylation	7
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
bisphenol A	decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases expression	3
perfluorooctanoic acid	increases expression	2
Cadmium	increases expression	2
Estradiol	increases expression	2
Hydrogen Peroxide	affects expression, increases oxidation	2
Ivermectin	affects cotreatment, decreases expression	2
Silicon Dioxide	increases expression	2
Tretinoin	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
Glupearl 19S	increases expression	1
triphenyl phosphate	affects expression	1
glycidyl methacrylate	increases expression	1
lead acetate	increases phosphorylation, affects reaction, decreases expression, increases abundance, decreases phosphorylation (+1 more)	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
methylparaben	decreases expression	1
afimoxifene	decreases reaction, increases expression	1
sulforaphane	increases expression	1
butyraldehyde	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
ochratoxin A	increases expression, decreases reaction	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
pentanal	increases expression	1
celastrol	decreases expression	1
di-n-butylphosphoric acid	affects expression	1

ChEMBL screening assays

12 unique, capped per target: 12 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3367168	Binding	Binding affinity to cyclophilin D (unknown origin)	From chemical tools to clinical medicines: nonimmunosuppressive cyclophilin inhibitors derived from the cyclosporin and sanglifehrin scaffolds. — J Med Chem

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3ED	Abcam HEK293T PPIF KO	Transformed cell line	Female
CVCL_D8FC	Ubigene Caco-2 PPIF KO	Cancer cell line	Male
CVCL_TF30	HAP1 PPIF (-) 1	Cancer cell line	Male
CVCL_TF31	HAP1 PPIF (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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