Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYKLW1K)

• DOT Name: Peptidyl-prolyl cis-trans isomerase FKBP10 (FKBP10)
• Synonyms: PPIase FKBP10; EC 5.2.1.8; 65 kDa FK506-binding protein; 65 kDa FKBP; FKBP-65; FK506-binding protein 10; FKBP-10; Immunophilin FKBP65; Rotamase
• Gene Name: FKBP10
• Related Disease:
  Osteogenesis imperfecta type 11
  Bruck syndrome 1
  Arthrogryposis-like syndrome
  Bruck syndrome
  Osteogenesis imperfecta type 3
  Osteogenesis imperfecta type 4
• UniProt ID: FKB10_HUMAN
• EC Number: 5.2.1.8
• Pfam ID: PF13202 ; PF00254
• Sequence:
  MFPAGPPSHSLLRLPLLQLLLLVVQAVGRGLGRASPAGGPLEDVVIERYHIPRACPREVQ
  MGDFVRYHYNGTFEDGKKFDSSYDRNTLVAIVVGVGRLITGMDRGLMGMCVNERRRLIVP
  PHLGYGSIGLAGLIPPDATLYFDVVLLDVWNKEDTVQVSTLLRPPHCPRMVQDGDFVRYH
  YNGTLLDGTSFDTSYSKGGTYDTYVGSGWLIKGMDQGLLGMCPGERRKIIIPPFLAYGEK
  GYGTVIPPQASLVFHVLLIDVHNPKDAVQLETLELPPGCVRRAGAGDFMRYHYNGSLMDG
  TLFDSSYSRNHTYNTYIGQGYIIPGMDQGLQGACMGERRRITIPPHLAYGENGTGDKIPG
  SAVLIFNVHVIDFHNPADVVEIRTLSRPSETCNETTKLGDFVRYHYNCSLLDGTQLFTSH
  DYGAPQEATLGANKVIEGLDTGLQGMCVGERRQLIVPPHLAHGESGARGVPGSAVLLFEV
  ELVSREDGLPTGYLFVWHKDPPANLFEDMDLNKDGEVPPEEFSTFIKAQVSEGKGRLMPG
  QDPEKTIGDMFQNQDRNQDGKITVDELKLKSDEDEERVHEEL
• Function: PPIases accelerate the folding of proteins during protein synthesis.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Osteogenesis imperfecta type 11	DISZXR4O	Definitive	Autosomal recessive	[1]
Bruck syndrome 1	DISCLKVK	Strong	Autosomal recessive	[2]
Arthrogryposis-like syndrome	DISJRFBW	Supportive	Autosomal recessive	[3]
Bruck syndrome	DIS9PCZ6	Supportive	Autosomal recessive	[2]
Osteogenesis imperfecta type 3	DISFJVSJ	Supportive	Autosomal dominant	[4]
Osteogenesis imperfecta type 4	DIS8S46L	Supportive	Autosomal dominant	[4]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Peptidyl-prolyl cis-trans isomerase FKBP10 (FKBP10).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Peptidyl-prolyl cis-trans isomerase FKBP10 (FKBP10).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Peptidyl-prolyl cis-trans isomerase FKBP10 (FKBP10).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Peptidyl-prolyl cis-trans isomerase FKBP10 (FKBP10).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP10 (FKBP10).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP10 (FKBP10).	[9]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Peptidyl-prolyl cis-trans isomerase FKBP10 (FKBP10).	[10]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP10 (FKBP10).	[11]
Liothyronine	DM6IR3P	Approved	Liothyronine decreases the expression of Peptidyl-prolyl cis-trans isomerase FKBP10 (FKBP10).	[12]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP10 (FKBP10).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Peptidyl-prolyl cis-trans isomerase FKBP10 (FKBP10).	[15]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP10 (FKBP10).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Peptidyl-prolyl cis-trans isomerase FKBP10 (FKBP10).	[17]
GALLICACID	DM6Y3A0	Investigative	GALLICACID increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP10 (FKBP10).	[18]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP10 (FKBP10).	[19]

References

• [1] Mutations in the gene encoding the RER protein FKBP65 cause autosomal-recessive osteogenesis imperfecta. Am J Hum Genet. 2010 Apr 9;86(4):551-9. doi: 10.1016/j.ajhg.2010.02.022. Epub 2010 Apr 1.
• [2] A novel homozygous 5 bp deletion in FKBP10 causes clinically Bruck syndrome in an Indonesian patient. Eur J Med Genet. 2012 Jan;55(1):17-21. doi: 10.1016/j.ejmg.2011.10.002. Epub 2011 Oct 24.
• [3] Kuskokwim syndrome, a recessive congenital contracture disorder, extends the phenotype of FKBP10 mutations. Hum Mutat. 2013 Sep;34(9):1279-88. doi: 10.1002/humu.22362. Epub 2013 Jul 8.
• [4] 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.
• [5] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [6] 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.
• [7] 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.
• [8] Arsenic alters transcriptional responses to Pseudomonas aeruginosa infection and decreases antimicrobial defense of human airway epithelial cells. Toxicol Appl Pharmacol. 2017 Sep 15;331:154-163.
• [9] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [10] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [11] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [12] Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
• [13] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [14] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [15] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [16] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [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] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [19] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.