Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLPH6KN)

• DOT Name: Peptidyl-prolyl cis-trans isomerase B (PPIB)
• Synonyms: PPIase B; EC 5.2.1.8; CYP-S1; Cyclophilin B; Rotamase B; S-cyclophilin; SCYLP
• Gene Name: PPIB
• Related Disease:
  Osteogenesis imperfecta type 9
  Osteogenesis imperfecta type 2
  Osteogenesis imperfecta type 3
  Osteogenesis imperfecta type 4
• UniProt ID: PPIB_HUMAN
• PDB ID: 1CYN; 3ICH; 3ICI
• EC Number: 5.2.1.8
• Pfam ID: PF00160
• Sequence:
  MLRLSERNMKVLLAAALIAGSVFFLLLPGPSAADEKKKGPKVTVKVYFDLRIGDEDVGRV
  IFGLFGKTVPKTVDNFVALATGEKGFGYKNSKFHRVIKDFMIQGGDFTRGDGTGGKSIYG
  ERFPDENFKLKHYGPGWVSMANAGKDTNGSQFFITTVKTAWLDGKHVVFGKVLEGMEVVR
  KVESTKTDSRDKPLKDVIIADCGKIEVEKPFAIAKE
• Function: PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding.
• Reactome Pathway:
  SARS-CoV-1 activates/modulates innate immune responses (R-HSA-9692916)
  Collagen biosynthesis and modifying enzymes (R-HSA-1650814)
• BioCyc Pathway: MetaCyc:HS09452-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Osteogenesis imperfecta type 9	DISS7OBY	Strong	Autosomal recessive	[1]
Osteogenesis imperfecta type 2	DISMGSS3	Supportive	Autosomal dominant	[2]
Osteogenesis imperfecta type 3	DISFJVSJ	Supportive	Autosomal dominant	[2]
Osteogenesis imperfecta type 4	DIS8S46L	Supportive	Autosomal dominant	[3]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Peptidyl-prolyl cis-trans isomerase B (PPIB) affects the response to substance of Paclitaxel.	[20]

17 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Peptidyl-prolyl cis-trans isomerase B (PPIB).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Peptidyl-prolyl cis-trans isomerase B (PPIB).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Peptidyl-prolyl cis-trans isomerase B (PPIB).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Peptidyl-prolyl cis-trans isomerase B (PPIB).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Peptidyl-prolyl cis-trans isomerase B (PPIB).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Peptidyl-prolyl cis-trans isomerase B (PPIB).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Peptidyl-prolyl cis-trans isomerase B (PPIB).	[10]
Selenium	DM25CGV	Approved	Selenium increases the expression of Peptidyl-prolyl cis-trans isomerase B (PPIB).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Peptidyl-prolyl cis-trans isomerase B (PPIB).	[12]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Peptidyl-prolyl cis-trans isomerase B (PPIB).	[13]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Peptidyl-prolyl cis-trans isomerase B (PPIB).	[14]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Peptidyl-prolyl cis-trans isomerase B (PPIB).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Peptidyl-prolyl cis-trans isomerase B (PPIB).	[15]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Peptidyl-prolyl cis-trans isomerase B (PPIB).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Peptidyl-prolyl cis-trans isomerase B (PPIB).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Peptidyl-prolyl cis-trans isomerase B (PPIB).	[18]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Peptidyl-prolyl cis-trans isomerase B (PPIB).	[19]

References

• [1] PPIB mutations cause severe osteogenesis imperfecta. Am J Hum Genet. 2009 Oct;85(4):521-7. doi: 10.1016/j.ajhg.2009.09.001. Epub 2009 Sep 24.
• [2] Nosology and classification of genetic skeletal disorders: 2010 revision. Am J Med Genet A. 2011 May;155A(5):943-68. doi: 10.1002/ajmg.a.33909. Epub 2011 Mar 15.
• [3] Mutations in PPIB (cyclophilin B) delay type I procollagen chain association and result in perinatal lethal to moderate osteogenesis imperfecta phenotypes. Hum Mol Genet. 2011 Apr 15;20(8):1595-609. doi: 10.1093/hmg/ddr037. Epub 2011 Jan 31.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [10] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [11] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [12] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [13] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [14] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [15] Differential protein expression of peroxiredoxin I and II by benzo(a)pyrene and quercetin treatment in 22Rv1 and PrEC prostate cell lines. Toxicol Appl Pharmacol. 2007 Apr 15;220(2):197-210. doi: 10.1016/j.taap.2006.12.030. Epub 2007 Jan 9.
• [16] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [17] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [18] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [19] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [20] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.