Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJB2UTH)

• DOT Name: Androgen-induced gene 1 protein (AIG1)
• Synonyms: AIG-1; Fatty acid esters of hydroxy fatty acids hydrolase AIG1; FAHFA hydrolase AIG1; EC 3.1.-.-
• Gene Name: AIG1
• Related Disease: Neoplasm
• UniProt ID: AIG1_HUMAN
• EC Number: 3.1.-.-
• Pfam ID: PF04750
• Sequence:
  MALVPCQVLRMAILLSYCSILCNYKAIEMPSHQTYGGSWKFLTFIDLVIQAVFFGICVLT
  DLSSLLTRGSGNQEQERQLKKLISLRDWMLAVLAFPVGVFVVAVFWIIYAYDREMIYPKL
  LDNFIPGWLNHGMHTTVLPFILIEMRTSHHQYPSRSSGLTAICTFSVGYILWVCWVHHVT
  GMWVYPFLEHIGPGARIIFFGSTTILMNFLYLLGEVLNNYIWDTQKSMEEEKEKPKLE
• Function: Hydrolyzes bioactive fatty-acid esters of hydroxy-fatty acids (FAHFAs), but not other major classes of lipids. Show a preference for FAHFAs with branching distal from the carboxylate head group of the lipids.
• Tissue Specificity: Highly expressed in heart, ovary, testis, liver, and kidney, at lower levels in spleen, prostate, brain, skeletal muscle, pancreas, small intestine and colon, and undetected in peripheral blood leukocytes, thymus, lung and placenta. AIG1 expression is higher in hair follicles from males than from females.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorpyrifos	DMKPUI6	Investigative	Androgen-induced gene 1 protein (AIG1) decreases the response to substance of Chlorpyrifos.	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Androgen-induced gene 1 protein (AIG1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Androgen-induced gene 1 protein (AIG1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Androgen-induced gene 1 protein (AIG1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Androgen-induced gene 1 protein (AIG1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Androgen-induced gene 1 protein (AIG1).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Androgen-induced gene 1 protein (AIG1).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Androgen-induced gene 1 protein (AIG1).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Androgen-induced gene 1 protein (AIG1).	[9]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Androgen-induced gene 1 protein (AIG1).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Androgen-induced gene 1 protein (AIG1).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Androgen-induced gene 1 protein (AIG1).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Androgen-induced gene 1 protein (AIG1).	[2]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Androgen-induced gene 1 protein (AIG1).	[13]

References

• [1] Novel chromosomal rearrangements and break points at the t(6;9) in salivary adenoid cystic carcinoma: association with MYB-NFIB chimeric fusion, MYB expression, and clinical outcome.Clin Cancer Res. 2011 Nov 15;17(22):7003-14. doi: 10.1158/1078-0432.CCR-11-1870. Epub 2011 Oct 5.
• [2] 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.
• [3] 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.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [10] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [11] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [12] 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.
• [13] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [14] Application of human haploid cell genetic screening model in identifying the genes required for resistance to environmental toxicants: Chlorpyrifos as a case study. J Pharmacol Toxicol Methods. 2015 Nov-Dec;76:76-82. doi: 10.1016/j.vascn.2015.08.154. Epub 2015 Aug 20.