PPIB

Summary

PPIB (peptidylprolyl isomerase B, HGNC:9255) is a protein-coding gene on chromosome 15q22.31, encoding Peptidyl-prolyl cis-trans isomerase B (P23284). 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 cyclosporine-binding protein and is mainly located within the endoplasmic reticulum. It is associated with the secretory pathway and released in biological fluids. This protein can bind to cells derived from T- and B-lymphocytes, and may regulate cyclosporine A-mediated immunosuppression. Variants have been identified in this protein that give rise to recessive forms of osteogenesis imperfecta.

Source: NCBI Gene 5479 — RefSeq curated summary.

At a glance

• Gene–disease (curated): osteogenesis imperfecta type 9 (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 193 total — 4 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 35
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000942

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9255
Approved symbol	PPIB
Name	peptidylprolyl isomerase B
Location	15q22.31
Locus type	gene with protein product
Status	Approved
Aliases	CYPB, OI9, PPIase, B, CYP-S1, SCYLP
Ensembl gene	ENSG00000166794
Ensembl biotype	protein_coding
OMIM	123841
Entrez	5479

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 18 protein_coding, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000300026, ENST00000558492, ENST00000561048, ENST00000680158, ENST00000680343, ENST00000681397, ENST00000681658, ENST00000718122, ENST00000718123, ENST00000851556, ENST00000851557, ENST00000919162, ENST00000919163, ENST00000919164, ENST00000919165, ENST00000919166, ENST00000919167, ENST00000919168, ENST00000919169, ENST00000919170, ENST00000919171, ENST00000919172, ENST00000919173

RefSeq mRNA: 1 — MANE Select: NM_000942 NM_000942

CCDS: CCDS10191

Canonical transcript exons

ENST00000300026 — 5 exons

Exon	Start	End
ENSE00001106702	64156725	64156909
ENSE00003563048	64162041	64162154
ENSE00003665606	64160104	64160197
ENSE00004034207	64155817	64156145
ENSE00004034210	64162852	64163022

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 753.5851 / max 5497.5767, expressed in 1827 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150465	751.7769	1827
150464	1.8082	1092

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.81	gold quality
corpus epididymis	UBERON:0004359	99.78	gold quality
caput epididymis	UBERON:0004358	99.70	gold quality
pituitary gland	UBERON:0000007	99.61	gold quality
seminal vesicle	UBERON:0000998	99.61	gold quality
right lobe of thyroid gland	UBERON:0001119	99.61	gold quality
adenohypophysis	UBERON:0002196	99.61	gold quality
left lobe of thyroid gland	UBERON:0001120	99.60	gold quality
parotid gland	UBERON:0001831	99.59	gold quality
cauda epididymis	UBERON:0004360	99.59	gold quality
pericardium	UBERON:0002407	99.58	gold quality
islet of Langerhans	UBERON:0000006	99.57	gold quality
endocervix	UBERON:0000458	99.55	gold quality
body of pancreas	UBERON:0001150	99.55	gold quality
smooth muscle tissue	UBERON:0001135	99.54	gold quality
cartilage tissue	UBERON:0002418	99.53	gold quality
gall bladder	UBERON:0002110	99.49	gold quality
right ovary	UBERON:0002118	99.49	gold quality
thyroid gland	UBERON:0002046	99.46	gold quality
left ovary	UBERON:0002119	99.46	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.46	gold quality
left adrenal gland	UBERON:0001234	99.45	gold quality
upper lobe of lung	UBERON:0008948	99.44	gold quality
metanephros cortex	UBERON:0010533	99.44	gold quality
upper lobe of left lung	UBERON:0008952	99.43	gold quality
left adrenal gland cortex	UBERON:0035825	99.43	gold quality
ascending aorta	UBERON:0001496	99.42	gold quality
thoracic aorta	UBERON:0001515	99.42	gold quality
placenta	UBERON:0001987	99.42	gold quality
right adrenal gland	UBERON:0001233	99.41	gold quality

Single-cell (SCXA)

Detected in 31 experiment(s), a significant marker in 23.

Experiment	Marker?	Max mean expression
E-CURD-77	yes	3468.19
E-CURD-55	yes	3386.68
E-MTAB-9221	yes	2922.06
E-CURD-122	yes	2854.95
E-MTAB-9467	yes	2774.76
E-GEOD-149689	yes	2017.55
E-MTAB-6386	yes	1763.03
E-GEOD-111727	yes	1624.60
E-MTAB-10042	yes	1353.71
E-MTAB-10287	yes	106.46
E-HCAD-1	yes	83.37
E-HCAD-4	yes	62.73
E-HCAD-6	yes	37.28
E-MTAB-8410	yes	35.06
E-CURD-112	yes	32.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting PPIB, 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-8068	99.98	73.85	2376
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-5587-5P	99.07	68.58	838
HSA-MIR-8066	99.05	68.66	1532
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-7114-5P	98.51	67.87	1349
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-5194	96.77	63.91	1021
HSA-MIR-668-3P	96.18	65.80	673
HSA-MIR-6734-5P	95.70	65.56	950
HSA-MIR-2861	95.24	65.47	1056

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• calcium signaling through CD147 receptor; induces neutrophil chemotaxis (PMID:11688976)
• act in the context of t lymphocyte recruitment and function (PMID:11867726)
• Different regions of CyPB are involved in peripheral blood T-lymphocyte activation and imply an important physiological function for peptidylprolyl isomerase activity. (PMID:11955071)
• Inhibition of the PT-pore (ANT-1) via up-regulation of cyclophilin D plays a role in tumorigenesis (PMID:14729611)
• Cyclophilin B plays a critical role in the activation of interferon regulatory factor-3. (PMID:15764595)
• CYPB is a functional rfegulator of hepacivirus RNA polymerase. (PMID:15989969)
• results strongly support the hypothesis that 3-O-sulfation of GlcNH2 residues could be a key modification that provides specialized HS structures for CyPB binding to responsive cells (PMID:17588944)
• Altogether, our results support a model whereby CyPB induces integrin-mediated adhesion via interaction with a multimolecular unit formed by the association between CD147, CD98 and beta1 integrins. (PMID:18054915)
• CypB is a new TRPV6 accessory protein with potential involvement in TRPV6 channel activation through its peptidyl-prolyl cis/trans isomerase activity (PMID:18445599)
• the enhanced expression of CypB in malignant breast epithelium may contribute to the pathogenesis of this disease (PMID:19056847)
• many proline residues in NS5A-D2 form a valid substrate for the enzymatic peptidyl-prolyl cis/trans isomerase (PPIase) activity of CypA and CypB. (PMID:19297321)
• Data show thatCypA and CypB both play pivotal roles, yet at different signaling levels, for Stat3 activation and function. (PMID:19503092)
• PPIB mutations cause severe osteogenesis imperfecta (PMID:19781681)
• a regulatory mechanism in which cell type-specific expression of certain heparan sulfate sulfotransferases determines the specific binding of CyPB to target cells (PMID:19940140)
• Cyclophilin B significantly modulate prolactin-induced function in breast cancer cells, ultimately resulting in enhanced levels of prolactin-responsive gene expression, cell growth, and migration. (PMID:20237142)
• Results reveal the P-domain functions as a unique protein-protein interaction domain and implicate a peptidyl prolyl isomerase as a new element in the calnexin cycle. (PMID:20801878)
• Data indicate that CypB through its interaction with Na/K-beta1 might regulate maturation and trafficking of the pump through the secretory pathway. (PMID:21085665)
• cyclophilin isoform B is likely responsible for down-regulation of carrier expression by CsA and that it does so via its chaperone activity on NaDC1 (by direct interaction) rather than its rotamase activity. (PMID:21257749)
• These results suggest that CypB plays a crucial role in the replication of Japanese encephalitis virus through an interaction with NS4A. (PMID:21281954)
• peptidylprolyl cis-trans isomerase B may be required to effectively fold the proline-rich regions of the C-terminal propeptide of procollagen (PMID:21282188)
• CAHL is a CsA associated helicase-like protein, which would form trimer complex with cyclophilin B and NS5B of HCV (PMID:21559518)
• CypB induced by hypoxia stimulates the survival of hepatocellular carcinoma via a positive feedback loop with HIF-1alpha. (PMID:21748762)
• First report of a unique, multicomponent, high-capacity milk fat reservoir of prolactin as a bilayer-bound complex with cyclophilins A and B in human milk. (PMID:22205628)
• CypB interacts with these proteins and is involved in ribosome biogenesis and RNA transcription. (PMID:22426501)
• Cyclophilin B is a candidate pancreatic cancer biomarker. (PMID:22484812)
• CypB has an essential function in protecting hepatoma cells against oxidative stress through binding to CD147 and regulating the ERK pathway (PMID:22555451)
• these findings suggest an unexpected role for cyclophilin B in attenuation of the responses of proinflammatory macrophages (PMID:22798670)
• Cyclophilin B activity regulated secretion and activity of ADAMTS13. (PMID:23144461)
• An additional function of the rough endoplasmic reticulum protein complex prolyl 3-hydroxylase 1.cartilage-associated protein.cyclophilin B: the CXXXC motif reveals disulfide isomerase activity in vitro. (PMID:24043621)
• Findings demonstrate that CypB prevents hypoxia-induced cell death through modulation of ubiquitin-mediated CHOP protein degradation, suggesting that CypB may have an important role in the tight regulation of CHOP under hypoxia. (PMID:24270407)
• cyclophilin B (CypB) is a prolyl isomerase residing in the endoplasmic reticulum (ER), that provides an essential survival signal in glioblastoma multiforme cells through myc and mutant p53 (PMID:24272483)
• Cyclophilin B is a novel MDM2 interacting partner. (PMID:24583282)
• The extracellular portion of cyclophilin B probably plays an important role in human diseases associated with acute or chronic inflammation (PMID:24713575)
• These findings establish cyclophilin C as an ER cyclophilin, demonstrate the novel involvement of cyclophilins B and C in ER redox homeostasis (PMID:24990953)
• Cyclophilin B has a high diagnostic value for stomach cancer and its downregulation can effectively inhibit the growth of stomach cancer cells. Thus, cyclophilin B may be a potential therapeutic target for stomach cancer treatment (PMID:26125731)
• This study enhances our knowledge about the mutational pattern of the LEPRE1, CRTAP, and PPIB genes. LEPRE1 should be the first gene analyzed in mutation detection studies in patients with recessive OI. (PMID:26634552)
• Over-expression of CypB enhances HIV infection by increasing nuclear import of viral DNA. (PMID:26774171)
• The data suggest that overexpressed CypB protects neuronal cells from MPP+-induced dopaminergic neuronal cell death (PMID:27569281)
• cyclophilin B (CYPB) functions in protecting cells against aldosterone-induced oxidative stress, endoplasmic reticulum stress (ERS) and tubular cell injury via its peptidyl-prolyl cis-trans isomerase (PPIase) activity. (PMID:27732567)
• PPIB mutations and their associated phenotypes (PMID:28242392)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppib	ENSDARG00000092798
mus_musculus	Ppib	ENSMUSG00000032383
rattus_norvegicus	Ppib	ENSRNOG00000016781
drosophila_melanogaster	Cyp40	FBGN0036020
caenorhabditis_elegans		WBGENE00000885

Paralogs (22): PPIE (ENSG00000084072), PPIL2 (ENSG00000100023), PPIF (ENSG00000108179), PPWD1 (ENSG00000113593), NKTR (ENSG00000114857), PPIL4 (ENSG00000131013), PPIL1 (ENSG00000137168), PPIG (ENSG00000138398), CWC27 (ENSG00000153015), 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 B — P23284 (reviewed: P23284)

Alternative names: CYP-S1, Cyclophilin B, Rotamase B, S-cyclophilin

All UniProt accessions (4): P23284, A0A7P0T7U3, A0A7P0TB45, A0A7P0Z497

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.

Subunit / interactions. Interacts with DYM. Interacts with CALR, CLGN and CANX. Part of a large chaperone multiprotein complex comprising DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1 and very small amounts of ERP29, but not, or at very low levels, CALR nor CANX. (Microbial infection) Interacts with measles virus nucleoprotein.

Subcellular location. Virion Endoplasmic reticulum lumen. Melanosome.

Disease relevance. Osteogenesis imperfecta 9 (OI9) [MIM:259440] A form of osteogenesis imperfecta, a disorder of bone formation characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI9 is a severe autosomal recessive form of the disorder. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by cyclosporin A (CsA).

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

RefSeq proteins (1): NP_000933* (*=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 (35 total): strand 12, turn 5, modified residue 5, helix 3, sequence variant 2, sequence conflict 2, signal peptide 1, chain 1, mutagenesis site 1, domain 1, short sequence motif 1, glycosylation site 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
3ICH	X-RAY DIFFRACTION	1.2
3ICI	X-RAY DIFFRACTION	1.7
1CYN	X-RAY DIFFRACTION	1.85
8K0M	ELECTRON MICROSCOPY	3.17
8K17	ELECTRON MICROSCOPY	3.18
8K0F	ELECTRON MICROSCOPY	3.37
8K0I	ELECTRON MICROSCOPY	3.62
8KC9	ELECTRON MICROSCOPY	3.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23284-F1	91.98	0.83

Functional residue map

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

Post-translational modifications (5): 84, 165, 202, 209, 209

Glycosylation sites (1): 148

Mutagenesis-validated functional residues (1):

Position	Phenotype
129	impairs interaction with clgn and canx.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1650814	Collagen biosynthesis and modifying enzymes
R-HSA-9692916	SARS-CoV-1 activates/modulates innate immune responses

MSigDB gene sets: 332 (showing top): GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, MODULE_151, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_GROWTH, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GOBP_HOST_MEDIATED_PERTURBATION_OF_VIRAL_PROCESS, GOBP_LEUKOCYTE_CHEMOTAXIS, GOBP_TAXIS, GOBP_LEUKOCYTE_MIGRATION, GOBP_REGULATION_OF_MULTICELLULAR_ORGANISM_GROWTH, GOBP_BONE_DEVELOPMENT, GOBP_PROTEIN_MATURATION

GO Biological Process (8): protein folding (GO:0006457), neutrophil chemotaxis (GO:0030593), positive regulation of multicellular organism growth (GO:0040018), host-mediated activation of viral process (GO:0044794), host-mediated activation of viral genome replication (GO:0044829), protein stabilization (GO:0050821), bone development (GO:0060348), protein peptidyl-prolyl isomerization (GO:0000413)

GO Molecular Function (8): RNA binding (GO:0003723), peptidyl-prolyl cis-trans isomerase activity (GO:0003755), cyclosporin A binding (GO:0016018), obsolete unfolded protein binding (GO:0051082), RNA polymerase binding (GO:0070063), protein binding (GO:0005515), collagen binding (GO:0005518), isomerase activity (GO:0016853)

GO Cellular Component (14): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), smooth endoplasmic reticulum (GO:0005790), cytosol (GO:0005829), focal adhesion (GO:0005925), membrane (GO:0016020), protein-containing complex (GO:0032991), endoplasmic reticulum chaperone complex (GO:0034663), melanosome (GO:0042470), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Collagen formation	1
SARS-CoV-1-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	3
binding	2
intracellular membrane-bounded organelle	2
endoplasmic reticulum	2
cellular process	1
protein maturation	1
granulocyte chemotaxis	1
neutrophil migration	1
multicellular organism growth	1
regulation of multicellular organism growth	1
positive regulation of developmental growth	1
positive regulation of multicellular organismal process	1
host-mediated perturbation of viral process	1
host-mediated activation of viral process	1
host-mediated perturbation of viral genome replication	1
regulation of protein stability	1
skeletal system development	1
animal organ development	1
peptidyl-proline modification	1
nucleic acid binding	1
cis-trans isomerase activity	1
catalytic activity, acting on a protein	1
enzyme binding	1
protein-containing complex binding	1
catalytic activity	1
nuclear lumen	1
intracellular anatomical structure	1
endomembrane system	1
intracellular organelle lumen	1
cell-substrate junction	1
cellular_component	1
endoplasmic reticulum protein-containing complex	1
pigment granule	1
extracellular vesicle	1

Protein interactions and networks

STRING

4016 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPIB	P3H1	Q32P28	999
PPIB	CRTAP	O75718	999
PPIB	BSG	P35613	996
PPIB	HSP90B1	P14625	975
PPIB	PDIA4	P13667	974
PPIB	CALR	P27797	962
PPIB	CAMLG	P49069	961
PPIB	CANX	P27824	926
PPIB	DNAJB11	Q9UBS4	895
PPIB	HYOU1	Q9Y4L1	875
PPIB	FKBP10	Q96AY3	833
PPIB	P4HB	P07237	819
PPIB	P3H4	Q92791	818
PPIB	COL1A1	P02452	785
PPIB	HSPA5	P11021	784

IntAct

246 interactions, top by confidence:

A	B	Type	Score
SGTA	PPIB	psi-mi:“MI:0915”(physical association)	0.720
PPIB	PEX19	psi-mi:“MI:0915”(physical association)	0.720
PEX19	PPIB	psi-mi:“MI:0915”(physical association)	0.720
PPIB	SGTA	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PPIB	SGTB	psi-mi:“MI:0915”(physical association)	0.670
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
PDIA4	PPIB	psi-mi:“MI:0915”(physical association)	0.610
DYM	PPIB	psi-mi:“MI:0915”(physical association)	0.600
DYM	PPIB	psi-mi:“MI:0403”(colocalization)	0.600
COL1A1	CRTAP	psi-mi:“MI:0915”(physical association)	0.580
BANP	PPIB	psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	PPIB	psi-mi:“MI:0915”(physical association)	0.560
PPIB	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
PPIB	BANP	psi-mi:“MI:0915”(physical association)	0.560
PPIB		psi-mi:“MI:0915”(physical association)	0.560
PPIB	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (456): PEX19 (Two-hybrid), SGTA (Two-hybrid), UBQLN1 (Two-hybrid), BANP (Two-hybrid), PPIB (Affinity Capture-RNA), PPIB (Protein-peptide), PPIB (Affinity Capture-MS), PPIB (Affinity Capture-MS), PPIB (Affinity Capture-MS), PPIB (Affinity Capture-MS), PPIB (Affinity Capture-MS), PPIB (Affinity Capture-MS), PPIB (Affinity Capture-MS), PPIB (Reconstituted Complex), ALDOC (Co-fractionation)

ESM2 similar proteins: B3A0R0, D4AY02, O43447, O49605, O74729, O93826, O94273, P0C1H9, P0C1I0, P0C1I3, P0CP78, P0CP79, P0CP82, P0CP83, P15425, P23284, P23285, P24368, P24369, P25719, P28517, P30412, P35176, P45877, P52013, P52014, P52018, P80311, P84343, Q01490, Q08E11, Q0P5D0, Q26551, Q27774, Q2TZ33, Q2UGK2, Q4I5R9, Q4IPH4, Q4P6X6, Q4WCM6

Diamond homologs: A0A0R0H9T5, A2AR02, A8X8D0, D4AY02, O49886, O55035, O74729, O93826, O94273, P0C1H7, P0C1H9, P0C1I1, P0C1I2, P0C1I3, P0C1I7, P0C1I8, P0C1I9, P0CP82, P0CP83, P14088, P14832, P18253, P21568, P21569, P23284, P24367, P24368, P24369, P24525, P25007, P25719, P26882, P30414, P30415, P34790, P34791, P34887, P35627, P52009, P52010

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	10
Uncertain significance	76
Likely benign	66
Benign	8

Top pathogenic / likely-pathogenic (14)

Variant ID	HGVS	Classification
31843	NM_000942.5(PPIB):c.120del (p.Val42fs)	Pathogenic
31845	NM_000942.5(PPIB):c.343+1G>A	Pathogenic
3612403	NM_000942.5(PPIB):c.151C>T (p.Arg51Ter)	Pathogenic
3721567	NM_000942.5(PPIB):c.439_440del (p.Thr147fs)	Pathogenic
1300581	NM_000942.5(PPIB):c.243_244delinsC (p.Gly82fs)	Likely pathogenic
1910582	NM_000942.5(PPIB):c.313G>C (p.Gly105Arg)	Likely pathogenic
2835451	NM_000942.5(PPIB):c.249+1G>A	Likely pathogenic
3339830	NM_000942.5(PPIB):c.26T>A (p.Met9Lys)	Likely pathogenic
3577594	NM_000942.5(PPIB):c.269del (p.Asn90fs)	Likely pathogenic
3577595	NM_000942.5(PPIB):c.25A>G (p.Met9Val)	Likely pathogenic
3577596	NM_000942.5(PPIB):c.1A>T (p.Met1Leu)	Likely pathogenic
423387	NM_000942.5(PPIB):c.414_417dup (p.Met140fs)	Likely pathogenic
4689501	NM_000942.5(PPIB):c.497A>C (p.His166Pro)	Likely pathogenic
4819370	NM_000942.5(PPIB):c.358_359dup (p.Glu121fs)	Likely pathogenic

SpliceAI

689 predictions. Top by Δscore:

Variant	Effect	Δscore
15:64156141:ACCTC:A	acceptor_gain	1.0000
15:64156142:CCTCC:C	acceptor_gain	1.0000
15:64156143:CTC:C	acceptor_gain	1.0000
15:64156146:CTGGA:C	acceptor_loss	1.0000
15:64156147:T:C	acceptor_loss	1.0000
15:64156719:ACT:A	donor_loss	1.0000
15:64156721:T:TA	donor_loss	1.0000
15:64156722:C:CC	donor_loss	1.0000
15:64156723:A:T	donor_loss	1.0000
15:64156724:CCATG:C	donor_gain	1.0000
15:64156751:C:CT	donor_gain	1.0000
15:64156905:CTTTC:C	acceptor_gain	1.0000
15:64156906:TTTC:T	acceptor_gain	1.0000
15:64156908:TC:T	acceptor_gain	1.0000
15:64156909:CC:C	acceptor_gain	1.0000
15:64156910:C:CC	acceptor_gain	1.0000
15:64160099:GTTA:G	donor_loss	1.0000
15:64160102:A:T	donor_loss	1.0000
15:64160102:ACCT:A	donor_gain	1.0000
15:64160103:C:CG	donor_loss	1.0000
15:64160103:CCTC:C	donor_gain	1.0000
15:64160105:T:TA	donor_gain	1.0000
15:64160119:C:A	donor_gain	1.0000
15:64160194:CTTT:C	acceptor_gain	1.0000
15:64160196:TT:T	acceptor_gain	1.0000
15:64160196:TTC:T	acceptor_loss	1.0000
15:64160198:C:CC	acceptor_gain	1.0000
15:64160198:C:CG	acceptor_loss	1.0000
15:64162036:CTTA:C	donor_loss	1.0000
15:64162037:TTAC:T	donor_loss	1.0000

AlphaMissense

1423 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:64160130:T:A	D106V	1.000
15:64160131:C:G	D106H	1.000
15:64160147:G:C	F100L	1.000
15:64160147:G:T	F100L	1.000
15:64160149:A:G	F100L	1.000
15:64160163:C:G	R95P	1.000
15:64160164:G:T	R95S	1.000
15:64160167:G:C	H94D	1.000
15:64156744:C:T	G170D	0.999
15:64156755:A:C	H166Q	0.999
15:64156755:A:T	H166Q	0.999
15:64156768:A:G	L162P	0.999
15:64156768:A:T	L162Q	0.999
15:64156772:A:G	W161R	0.999
15:64156772:A:T	W161R	0.999
15:64156794:G:C	F153L	0.999
15:64156794:G:T	F153L	0.999
15:64156796:A:G	F153L	0.999
15:64156797:G:C	F152L	0.999
15:64156797:G:T	F152L	0.999
15:64156798:A:G	F152S	0.999
15:64156799:A:G	F152L	0.999
15:64156800:C:A	Q151H	0.999
15:64156800:C:G	Q151H	0.999
15:64156809:G:C	N148K	0.999
15:64156809:G:T	N148K	0.999
15:64156813:G:A	T147I	0.999
15:64156827:G:C	N142K	0.999
15:64156827:G:T	N142K	0.999
15:64156831:G:T	A141D	0.999

dbSNP variants (sampled 300 via entrez): RS1000176299 (15:64160063 C>G), RS1000367198 (15:64159728 C>G), RS1000420978 (15:64159427 G>A,C), RS1001190341 (15:64164151 G>A), RS1002123239 (15:64155739 A>C), RS1002335645 (15:64157340 A>G), RS1002611429 (15:64162975 G>A), RS1003209056 (15:64161846 A>C), RS1003533452 (15:64157115 G>A), RS1004206724 (15:64156984 G>A,C), RS1004894076 (15:64157380 A>G), RS1005144213 (15:64156019 T>C), RS1005229364 (15:64161909 C>T), RS1005678259 (15:64162309 A>C,G), RS1006181239 (15:64161029 C>T)

Disease associations

OMIM: gene MIM:123841 | disease phenotypes: MIM:259440, MIM:166200, MIM:259420

GenCC curated gene-disease

Disease	Classification	Inheritance
osteogenesis imperfecta type 9	Strong	Autosomal recessive
osteogenesis imperfecta type 2	Supportive	Autosomal dominant
osteogenesis imperfecta type 3	Supportive	Autosomal dominant
osteogenesis imperfecta type 4	Supportive	Autosomal dominant

Mondo (5): osteogenesis imperfecta type 9 (MONDO:0009805), osteogenesis imperfecta (MONDO:0019019), osteogenesis imperfecta type 3 (MONDO:0009804), osteogenesis imperfecta type 2 (MONDO:0008147), osteogenesis imperfecta type 4 (MONDO:0008148)

Orphanet (2): Osteogenesis imperfecta (Orphanet:666), Osteogenesis imperfecta type 3 (Orphanet:216812)

HPO phenotypes

35 total (30 of 35 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000260	Wide anterior fontanel
HP:0000325	Triangular face
HP:0000520	Proptosis
HP:0000592	Blue sclerae
HP:0000703	Dentinogenesis imperfecta
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0000774	Narrow chest
HP:0000926	Platyspondyly
HP:0000938	Osteopenia
HP:0000939	Osteoporosis
HP:0001537	Umbilical hernia
HP:0001763	Pes planus
HP:0002194	Delayed gross motor development
HP:0002540	Inability to walk
HP:0002645	Wormian bones
HP:0002650	Scoliosis
HP:0002757	Recurrent fractures
HP:0002808	Kyphosis
HP:0002953	Vertebral compression fracture
HP:0003023	Bowing of limbs due to multiple fractures
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0005019	Diaphyseal undertubulation
HP:0005469	Flat occiput
HP:0005474	Decreased calvarial ossification
HP:0005855	Multiple prenatal fractures
HP:0006094	Finger joint hypermobility
HP:0006385	Short lower limbs

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST007847_29	Type 2 diabetes	1.000000e-87
GCST010118_105	Type 2 diabetes	7.000000e-33
GCST010118_172	Type 2 diabetes	4.000000e-164
GCST010984_18	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	1.000000e-13

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D010013	Osteogenesis Imperfecta	C05.116.099.708.685; C16.320.737; C17.300.200.540
C564921	Osteogenesis Imperfecta, Type IX (supp.)
C536042	Osteogenesis imperfecta, type 2A (supp.)
C536044	Osteogenesis imperfecta, type 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2075 (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)

116 measured of 125 human assays (125 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
(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
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	KD	1.3 nM	US-9566312: Cyclic peptides and use as medicines

ChEMBL bioactivities

145 potent at pChembl≥5 of 152 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	Kd	0.3	nM	CHEMBL5812164
9.40	Kd	0.4	nM	CHEMBL5994784
9.40	Kd	0.4	nM	CHEMBL6062788
9.40	Kd	0.4	nM	CHEMBL5810211
9.40	Kd	0.4	nM	CHEMBL6051666
9.40	Kd	0.4	nM	CHEMBL5759368
9.40	Kd	0.4	nM	CHEMBL5842043
9.40	Kd	0.4	nM	CHEMBL6059588
9.40	Kd	0.4	nM	CHEMBL6048373
9.40	Kd	0.4	nM	CHEMBL5741417
9.30	Kd	0.5	nM	CHEMBL5831563
9.30	Kd	0.5	nM	CHEMBL6056488
9.30	Kd	0.5	nM	CHEMBL5791301
9.30	Kd	0.5	nM	CHEMBL5792144
9.30	Kd	0.5	nM	CHEMBL5992700
9.30	Kd	0.5	nM	CHEMBL3344493
9.30	Kd	0.5	nM	CHEMBL5798116
9.30	Kd	0.5	nM	CHEMBL5942857
9.30	Kd	0.5	nM	CHEMBL3344501
9.30	Kd	0.5	nM	CHEMBL6003202
9.30	Kd	0.5	nM	CHEMBL6010886
9.30	Kd	0.5	nM	CHEMBL6058387
9.30	Kd	0.5	nM	CHEMBL5757514
9.30	Kd	0.5	nM	CHEMBL5856868
9.22	Kd	0.6	nM	CHEMBL5988852
9.22	Kd	0.6	nM	CHEMBL6061966
9.22	Kd	0.6	nM	CHEMBL6050788
9.22	Kd	0.6	nM	CHEMBL5877920
9.22	Kd	0.6	nM	CHEMBL6038296
9.22	Kd	0.6	nM	CHEMBL5976250
9.22	Kd	0.6	nM	CHEMBL5867542
9.22	Kd	0.6	nM	CHEMBL6023421
9.22	Kd	0.6	nM	CHEMBL6044098
9.15	Kd	0.7	nM	CHEMBL5974662
9.15	Kd	0.7	nM	CHEMBL6062808
9.15	Kd	0.7	nM	CHEMBL5962188
9.15	Kd	0.7	nM	CHEMBL6046692
9.15	Kd	0.7	nM	CHEMBL5922149
9.15	Kd	0.7	nM	CHEMBL5821248
9.15	Kd	0.7	nM	CHEMBL6037963
9.15	Kd	0.7	nM	CHEMBL5757253
9.15	Kd	0.7	nM	CHEMBL5967576
9.15	Kd	0.7	nM	CHEMBL5902225
9.15	Kd	0.7	nM	CHEMBL5960352
9.15	Kd	0.7	nM	CHEMBL5983054
9.15	Kd	0.7	nM	CHEMBL5859080
9.15	Kd	0.7	nM	CHEMBL5926312
9.15	Kd	0.7	nM	CHEMBL5812196
9.15	Kd	0.7	nM	CHEMBL5866658
9.15	Kd	0.7	nM	CHEMBL6018548

PubChem BioAssay actives

33 with measured affinity, of 53 total; 30 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	1168835: Binding affinity to human cyclophilin B by surface plasmon resonance method	kd	0.0010	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	1168835: Binding affinity to human cyclophilin B by surface plasmon resonance method	kd	0.0012	uM
N-cyclohexyl-2-(N-[2-(1H-indol-3-yl)acetyl]-4-propan-2-ylanilino)-2-(3,4,5-trimethoxyphenyl)acetamide	1271124: Binding affinity to Cyclophilin B (unknown origin) at 10 to 30 uM by surface plasmon resonance analysis	kd	0.0021	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	1168835: Binding affinity to human cyclophilin B by surface plasmon resonance method	kd	0.0029	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	1168835: Binding affinity to human cyclophilin B by surface plasmon resonance method	kd	0.0074	uM
cyclosporine	528323: Binding affinity to cyclophilin B by ELISA	ic50	0.0088	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	528323: Binding affinity to cyclophilin B by ELISA	ic50	0.0095	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	528323: Binding affinity to cyclophilin B by ELISA	ic50	0.0127	uM
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-12-[3-(diethylamino)propyl]-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	528323: Binding affinity to cyclophilin B by ELISA	ic50	0.0172	uM
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-12-[4-(diethylamino)butyl]-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	528323: Binding affinity to cyclophilin B by ELISA	ic50	0.0198	uM
N-[4-[(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]butyl]-2,2-dimethylpropanamide	528323: Binding affinity to cyclophilin B by ELISA	ic50	0.0206	uM
3-[(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]propanenitrile	528323: Binding affinity to cyclophilin B by ELISA	ic50	0.0242	uM
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-12-[(dimethylamino)methyl]-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	528323: Binding affinity to cyclophilin B by ELISA	ic50	0.0252	uM
N-[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]ethyl]-2,2-dimethylpropanamide	528323: Binding affinity to cyclophilin B by ELISA	ic50	0.0261	uM
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-12-[3-(dimethylamino)propyl]-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	528323: Binding affinity to cyclophilin B by ELISA	ic50	0.0289	uM
N-[3-[(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]propyl]-2,2-dimethylpropanamide	528323: Binding affinity to cyclophilin B by ELISA	ic50	0.0305	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	770487: Inhibition of CypB PPIase activity (unknown origin)	ki	0.0352	uM
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-12-[2-(diethylamino)ethyl]-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	528323: Binding affinity to cyclophilin B by ELISA	ic50	0.0559	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149041: Binding affinity to human PPIB incubated for 45 mins by Kinobead based pull down assay	kd	0.0592	uM
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-12-[2-(dimethylamino)ethyl]-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	528323: Binding affinity to cyclophilin B by ELISA	ic50	0.0595	uM
tert-butyl N-[[(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]methyl]carbamate	528323: Binding affinity to cyclophilin B by ELISA	ic50	0.0668	uM
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-12-(aminomethyl)-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	528323: Binding affinity to cyclophilin B by ELISA	ic50	0.0797	uM
1-[(4-aminophenyl)methyl]-3-[2-[2-(2-methylsulfanylphenyl)pyrrolidin-1-yl]-2-oxo-1-phenylethyl]urea	1674212: Inhibition of C-terminal His6-tagged CypB (unknown origin) expressed in Escherichia coli C41(DE3) using Suc-Ala-Ala-Cis-Pro-Phe-pNA as substrate by spectrophotometric analysis	ic50	0.0800	uM
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-12-[4-(dimethylamino)butyl]-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	528323: Binding affinity to cyclophilin B by ELISA	ic50	0.0971	uM
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-12-(2-aminoethyl)-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	528323: Binding affinity to cyclophilin B by ELISA	ic50	0.1510	uM
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-12-(diethylaminomethyl)-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	528323: Binding affinity to cyclophilin B by ELISA	ic50	0.1580	uM
(3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-12-(3-aminopropyl)-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	528323: Binding affinity to cyclophilin B by ELISA	ic50	1.5830	uM
2,3-dihydro-1H-inden-1-yl-[2-methoxy-5-[4-(trifluoromethoxy)phenyl]phenyl]methanone	1799858: PPIase Assay from Article 10.1021/bi9007287: “Isoform-specific inhibition of cyclophilins.”	ki	2.1000	uM
ethyl 2-[(4-aminophenyl)methylcarbamoylamino]acetate	1674212: Inhibition of C-terminal His6-tagged CypB (unknown origin) expressed in Escherichia coli C41(DE3) using Suc-Ala-Ala-Cis-Pro-Phe-pNA as substrate by spectrophotometric analysis	ic50	6.1000	uM
[3-amino-5-(5-fluoro-2-methoxyphenyl)-2-hydroxyphenyl]-(2,3-dihydro-1H-inden-1-yl)methanone	1799858: PPIase Assay from Article 10.1021/bi9007287: “Isoform-specific inhibition of cyclophilins.”	ki	8.6000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	6
Cyclosporine	decreases expression, increases expression	4
bisphenol A	affects expression, decreases expression, increases expression	3
trichostatin A	increases expression, affects cotreatment	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tunicamycin	increases expression	2
Cadmium Chloride	decreases expression, decreases methylation, increases expression	2
bisphenol F	increases expression	1
beta-N-methylamino-L-alanine	increases expression	1
beauvericin	decreases expression	1
testosterone enanthate	affects expression	1
quinomethionate	affects expression	1
triphenyl phosphate	affects expression	1
glycidyl methacrylate	increases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, decreases expression, affects cotreatment	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	decreases expression	1
cupric oxide	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
JP8 aviation fuel	decreases expression	1
bisphenol B	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
NSC668394	increases expression	1
bisphenol AF	increases expression	1

ChEMBL screening assays

13 unique, capped per target: 13 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1012282	Binding	Binding affinity to human Cyclophilin B	Simultaneous identification of multiple receptors of natural product using an optimized cDNA phage display cloning. — Bioorg Med Chem Lett

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2BN	Abcam HeLa PPIB KO	Cancer cell line	Female
CVCL_TF29	HAP1 PPIB (-) 1	Cancer cell line	Male
CVCL_XR77	HAP1 PPIB (-) 2	Cancer cell line	Male
CVCL_XR78	HAP1 PPIB (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00131469	PHASE4	COMPLETED	Study of Teriparatide (FORTEO) to Treat Adults With Osteogenesis Imperfecta
NCT00159419	PHASE4	COMPLETED	Bisphosphonate Therapy for Osteogenesis Imperfecta
NCT01713231	PHASE4	COMPLETED	Effect of High-Dose Vitamin D on Bone Density in Osteogenesis Imperfecta
NCT02303873	PHASE4	COMPLETED	Efficacy and Safety of Alendronate in Chinese Children or Adolescents With Osteogenesis Imperfecta
NCT03735537	PHASE4	COMPLETED	Treatment of Osteogenesis Imperfecta With Parathyroid Hormone and Zoledronic Acid
NCT04152551	PHASE4	RECRUITING	Effects of Bisphosphonates on OI-Related Hearing Loss
NCT00001305	PHASE3	COMPLETED	Growth Hormone Therapy in Osteogenesis Imperfecta
NCT00005901	PHASE3	COMPLETED	Pamidronate to Treat Osteogenesis Imperfecta in Children
NCT00106028	PHASE3	COMPLETED	Safety and Efficacy of Risedronate in the Treatment of Osteogenesis Imperfecta in Children
NCT00982124	PHASE3	COMPLETED	An Efficacy and Safety Trial of Intravenous Zoledronic Acid in Infants Less Than One Year of Age, With Severe Osteogenesis Imperfecta
NCT02352753	PHASE3	TERMINATED	Multicenter,Single-arm Study to Evaluate Efficacy, Safety, & Pharmacokinetics of Denosumab in Children w/ OI
NCT03638128	PHASE3	TERMINATED	Open-label Extension of Study 20130173 of Denosumab in Children and Young Adults With Osteogenesis Imperfecta
NCT05768854	PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab vs Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta
NCT05972551	PHASE3	ACTIVE_NOT_RECRUITING	Study to Evaluate Efficacy and Safety of Romosozumab Compared With Bisphosphonates in Children and Adolescents With Osteogenesis Imperfecta
NCT06636071	PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab in Pediatric Japanese Subjects With Osteogenesis Imperfecta
NCT07366086	PHASE3	RECRUITING	Pediatric Safety Follow-up Study of Prior Treatment With Romosozumab for Osteogenesis Imperfecta
NCT03118570	PHASE2	COMPLETED	A Study in Adult Patients With Type I, III or IV Osteogenesis Imperfecta Treated With BPS804
NCT00063479	PHASE2	COMPLETED	Bisphosphonate Treatment of Osteogenesis Imperfecta
NCT00131118	PHASE2	COMPLETED	Zoledronic Acid in Children (1 -17 Years) With Severe Osteogenesis Imperfecta
NCT01417091	PHASE2	COMPLETED	Safety, Pharmacokinetics and Pharmacodynamics of BPS804 in Osteogenesis Imperfecta
NCT01679080	PHASE2	TERMINATED	The Effect of Treatment With Teriparatide and Zoledronic Acid in Patients With Osteogenesis Imperfecta
NCT01799798	PHASE2	COMPLETED	Translational Therapy in Patients With Osteogenesis Imperfecta - A Pilot Trial on Treatment With the Rankl-Antibody Denosumab
NCT03208582	PHASE2	COMPLETED	Do Bisphosphonates Alter the Skeletal Response to Mechanical Stimulation in Children With Osteogenesis Imperfecta?
NCT03216486	PHASE2	WITHDRAWN	An Exploratory Study of BPS804 Treatment in Adult Patients With Type I, III or IV Osteogenesis Imperfecta
NCT05312697	PHASE2	TERMINATED	Long-term Extension Study of Setrusumab in Adults With Type I, III, or IV Osteogenesis Imperfecta
NCT07062588	PHASE2	RECRUITING	Osteogenesis Imperfecta Trial of AGA2115 for ADUlts With COL1A1 and/or COL1A2 GeNetic Variations (IDUN)
NCT07557446	PHASE2	NOT_YET_RECRUITING	A Dose REgimen-Finding Study of AGA2115 in Chinese Patients With Osteogenesis ImpeRfecta (EIR)
NCT01061099	PHASE1	COMPLETED	Repeated Infusions of Mesenchymal Stromal Cells in Children With Osteogenesis Imperfecta
NCT00705120	PHASE1	COMPLETED	Treatment of Severe Osteogenesis Imperfecta by Allogeneic Bone Marrow Transplantation
NCT02172885	PHASE1	COMPLETED	Mesenchymal Stem Cell Based Therapy for the Treatment of Osteogenesis Imperfecta
NCT03064074	PHASE1	COMPLETED	Safety of Fresolimumab in the Treatment of Osteogenesis Imperfecta
NCT04545554	PHASE1	COMPLETED	Study to Evaluate Romosozumab in Children and Adolescents With Osteogenesis Imperfecta
NCT05231668	PHASE1	TERMINATED	Single Ascending Dose Study of SAR439459 in Adults With Osteogenesis Imperfecta (OI)
NCT06086613	PHASE1	COMPLETED	A First-in-Human Study Evaluating AGA2115 in Adult Healthy Volunteers
NCT05559801	PHASE1/PHASE2	NOT_YET_RECRUITING	Mesenchymal Cell Therapy in Osteogenesis Imperfecta (OI)
NCT05125809	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Setrusumab vs Placebo for Osteogenesis Imperfecta
NCT03706482	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Boost Brittle Bones Before Birth
NCT04623606	PHASE1/PHASE2	UNKNOWN	Boost to Brittle Bones - Stem Cell Transplantation for Treatment of Brittle Bones
NCT00001594	Not specified	COMPLETED	Evaluation and Intervention for the Effects of Osteogenesis Imperfecta
NCT00076830	Not specified	COMPLETED	Evaluation and Treatment of Patients With Connective Tissue Disease