Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW3GO4Y)

• DOT Name: Aflatoxin B1 aldehyde reductase member 3 (AKR7A3)
• Synonyms: EC 1.-.-.-; AFB1 aldehyde reductase 2; AFB1-AR 2
• Gene Name: AKR7A3
• Related Disease:
  Advanced cancer
  Hepatocellular carcinoma
  Neoplasm
• UniProt ID: ARK73_HUMAN
• PDB ID: 2CLP
• EC Number: 1.-.-.-
• Pfam ID: PF00248
• Sequence:
  MSRQLSRARPATVLGAMEMGRRMDAPTSAAVTRAFLERGHTEIDTAFVYSEGQSETILGG
  LGLRLGGSDCRVKIDTKAIPLFGNSLKPDSLRFQLETSLKRLQCPRVDLFYLHMPDHSTP
  VEETLRACHQLHQEGKFVELGLSNYAAWEVAEICTLCKSNGWILPTVYQGMYNAITRQVE
  TELFPCLRHFGLRFYAFNPLAGGLLTGKYKYEDKNGKQPVGRFFGNTWAEMYRNRYWKEH
  HFEGIALVEKALQAAYGASAPSMTSATLRWMYHHSQLQGAHGDAVILGMSSLEQLEQNLA
  AAEEGPLEPAVVDAFNQAWHLVTHECPNYFR
• Function: Can reduce the dialdehyde protein-binding form of aflatoxin B1 (AFB1) to the non-binding AFB1 dialcohol. May be involved in protection of liver against the toxic and carcinogenic effects of AFB1, a potent hepatocarcinogen.
• Tissue Specificity: Expressed in colon, kidney, liver, pancreas, adenocarcinoma and endometrium.
• KEGG Pathway: Metabolism of xenobiotics by cytochrome P450 (hsa00980)
• Reactome Pathway: Aflatoxin activation and detoxification (R-HSA-5423646)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	Limited	Biomarker	[2]

10 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 Aflatoxin B1 aldehyde reductase member 3 (AKR7A3).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Aflatoxin B1 aldehyde reductase member 3 (AKR7A3).	[4]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Aflatoxin B1 aldehyde reductase member 3 (AKR7A3).	[5]
Nefazodone	DM4ZS8M	Approved	Nefazodone decreases the expression of Aflatoxin B1 aldehyde reductase member 3 (AKR7A3).	[6]
Chenodiol	DMQ8JIK	Approved	Chenodiol decreases the expression of Aflatoxin B1 aldehyde reductase member 3 (AKR7A3).	[7]
Atazanavir	DMSYRBX	Approved	Atazanavir decreases the expression of Aflatoxin B1 aldehyde reductase member 3 (AKR7A3).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Aflatoxin B1 aldehyde reductase member 3 (AKR7A3).	[3]
EMODIN	DMAEDQG	Terminated	EMODIN decreases the activity of Aflatoxin B1 aldehyde reductase member 3 (AKR7A3).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Aflatoxin B1 aldehyde reductase member 3 (AKR7A3).	[9]
7-hydroxycoumarin	DMTMNO7	Investigative	7-hydroxycoumarin increases the expression of Aflatoxin B1 aldehyde reductase member 3 (AKR7A3).	[10]

References

• [1] Aldo-Keto Reductases as Early Biomarkers of Hepatocellular Carcinoma: A Comparison Between Animal Models and Human HCC.Dig Dis Sci. 2018 Apr;63(4):934-944. doi: 10.1007/s10620-018-4943-5. Epub 2018 Jan 30.
• [2] AKR7A3 suppresses tumorigenicity and chemoresistance in hepatocellular carcinoma through attenuation of ERK, c-Jun and NF-B signaling pathways.Oncotarget. 2016 Oct 18;8(48):83469-83479. doi: 10.18632/oncotarget.12726. eCollection 2017 Oct 13.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Effects of acute ethanol treatment on NCCIT cells and NCCIT cell-derived embryoid bodies (EBs). Toxicol In Vitro. 2010 Sep;24(6):1696-704. doi: 10.1016/j.tiv.2010.05.017. Epub 2010 May 26.
• [6] Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury. Arch Toxicol. 2020 Apr;94(4):1151-1172. doi: 10.1007/s00204-020-02691-9. Epub 2020 Mar 10.
• [7] Chenodeoxycholic acid significantly impacts the expression of miRNAs and genes involved in lipid, bile acid and drug metabolism in human hepatocytes. Life Sci. 2016 Jul 1;156:47-56.
• [8] Inhibition of human carbonyl reducing enzymes by plant anthrone and anthraquinone derivatives. Chem Biol Interact. 2022 Feb 25;354:109823. doi: 10.1016/j.cbi.2022.109823. Epub 2022 Jan 21.
• [9] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [10] Hepatoprotective effect of 7-hydroxycoumarin against methyl glyoxal toxicity via activation of Nrf2. Chem Biol Interact. 2017 Oct 1;276:203-209.