Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY2GC67)

• DOT Name: Peptidyl-prolyl cis-trans isomerase FKBP11 (FKBP11)
• Synonyms: PPIase FKBP11; EC 5.2.1.8; 19 kDa FK506-binding protein; 19 kDa FKBP; FKBP-19; FK506-binding protein 11; FKBP-11; Rotamase
• Gene Name: FKBP11
• Related Disease:
  Amyotrophic lateral sclerosis type 1
  Crohn disease
  Hemangioma
  Hepatitis A virus infection
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Neoplasm
  Viral hepatitis
• UniProt ID: FKB11_HUMAN
• EC Number: 5.2.1.8
• Pfam ID: PF00254
• Sequence:
  MTLRPSLLPLHLLLLLLLSAAVCRAEAGLETESPVRTLQVETLVEPPEPCAEPAAFGDTL
  HIHYTGSLVDGRIIDTSLTRDPLVIELGQKQVIPGLEQSLLDMCVGEKRRAIIPSHLAYG
  KRGFPPSVPADAVVQYDVELIALIRANYWLKLVKGILPLVGMAMVPALLGLIGYHLYRKA
  NRPKVSKKKLKEEKRNKSKKK
• Function: PPIases accelerate the folding of proteins during protein synthesis.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyotrophic lateral sclerosis type 1	DIS5A2M0	Strong	Biomarker	[1]
Crohn disease	DIS2C5Q8	Strong	Altered Expression	[2]
Hemangioma	DISDCGAG	Strong	Altered Expression	[3]
Hepatitis A virus infection	DISUMFQV	Strong	Altered Expression	[3]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Viral hepatitis	DISVT5Q7	Strong	Altered Expression	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Peptidyl-prolyl cis-trans isomerase FKBP11 (FKBP11) affects the response to substance of Fluorouracil.	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP11 (FKBP11).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP11 (FKBP11).	[6]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Peptidyl-prolyl cis-trans isomerase FKBP11 (FKBP11).	[7]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP11 (FKBP11).	[8]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP11 (FKBP11).	[9]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP11 (FKBP11).	[10]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP11 (FKBP11).	[11]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Peptidyl-prolyl cis-trans isomerase FKBP11 (FKBP11).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Peptidyl-prolyl cis-trans isomerase FKBP11 (FKBP11).	[14]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP11 (FKBP11).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP11 (FKBP11).	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Peptidyl-prolyl cis-trans isomerase FKBP11 (FKBP11).	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Peptidyl-prolyl cis-trans isomerase FKBP11 (FKBP11).	[12]

References

• [1] The role of immunophilins in mutant superoxide dismutase-1linked familial amyotrophic lateral sclerosis.Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):3251-6. doi: 10.1073/pnas.96.6.3251.
• [2] FKBP11 protects intestinal epithelial cells against inflammationinduced apoptosis via the JNKcaspase pathway in Crohn's disease.Mol Med Rep. 2018 Nov;18(5):4428-4438. doi: 10.3892/mmr.2018.9485. Epub 2018 Sep 14.
• [3] Identification of FKBP11 as a biomarker for hepatocellular carcinoma.Anticancer Res. 2013 Jun;33(6):2763-9.
• [4] c-Myc targeted regulators of cell metabolism in a transgenic mouse model of papillary lung adenocarcinoma.Oncotarget. 2016 Oct 4;7(40):65514-65539. doi: 10.18632/oncotarget.11804.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [7] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [8] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [9] Microarray analysis of bicalutamide action on telomerase activity, p53 pathway and viability of prostate carcinoma cell lines. J Pharm Pharmacol. 2005 Jan;57(1):83-92.
• [10] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [11] 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.
• [12] 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.
• [13] BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell. 2011 Sep 16;146(6):904-17.
• [14] 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.
• [15] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [16] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [17] 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.