Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR67PGU)

• DOT Name: Fas apoptotic inhibitory molecule 1 (FAIM)
• Gene Name: FAIM
• Related Disease: Nasopharyngeal carcinoma
• UniProt ID: FAIM1_HUMAN
• PDB ID: 2KW1; 3MX7
• Pfam ID: PF06905
• Sequence:
  MTDLVAVWDVALSDGVHKIEFEHGTTSGKRVVYVDGKEEIRKEWMFKLVGKETFYVGAAK
  TKATINIDAISGFAYEYTLEINGKSLKKYMEDRSKTTNTWVLHMDGENFRIVLEKDAMDV
  WCNGKKLETAGEFVDDGTETHFSIGNHDCYIKAVSSGKRKEGIIHTLIVDNREIPEIAS
• Function: Plays a role as an inducible effector molecule that mediates Fas resistance produced by surface Ig engagement in B cells.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Altered Expression	[1]

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 Fas apoptotic inhibitory molecule 1 (FAIM).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Fas apoptotic inhibitory molecule 1 (FAIM).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Fas apoptotic inhibitory molecule 1 (FAIM).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Fas apoptotic inhibitory molecule 1 (FAIM).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Fas apoptotic inhibitory molecule 1 (FAIM).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Fas apoptotic inhibitory molecule 1 (FAIM).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Fas apoptotic inhibitory molecule 1 (FAIM).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Fas apoptotic inhibitory molecule 1 (FAIM).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Fas apoptotic inhibitory molecule 1 (FAIM).	[9]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Fas apoptotic inhibitory molecule 1 (FAIM).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Fas apoptotic inhibitory molecule 1 (FAIM).	[11]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Fas apoptotic inhibitory molecule 1 (FAIM).	[12]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Fas apoptotic inhibitory molecule 1 (FAIM).	[13]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial decreases the expression of Fas apoptotic inhibitory molecule 1 (FAIM).	[14]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium decreases the expression of Fas apoptotic inhibitory molecule 1 (FAIM).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Fas apoptotic inhibitory molecule 1 (FAIM).	[15]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Fas apoptotic inhibitory molecule 1 (FAIM).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Fas apoptotic inhibitory molecule 1 (FAIM).	[18]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Fas apoptotic inhibitory molecule 1 (FAIM).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Fas apoptotic inhibitory molecule 1 (FAIM).	[20]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Fas apoptotic inhibitory molecule 1 (FAIM).	[21]

References

• [1] Genome-wide expression profiling reveals EBV-associated inhibition of MHC class I expression in nasopharyngeal carcinoma.Cancer Res. 2006 Aug 15;66(16):7999-8006. doi: 10.1158/0008-5472.CAN-05-4399.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [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] 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.
• [9] A genomic approach to predict synergistic combinations for breast cancer treatment. Pharmacogenomics J. 2013 Feb;13(1):94-104. doi: 10.1038/tpj.2011.48. Epub 2011 Nov 15.
• [10] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [11] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [12] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [13] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [14] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [19] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [20] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [21] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.