Details of Drug Off-Target (DOT)

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

• DOT Name: Cytochrome P450 3A43 (CYP3A43)
• Synonyms: EC 1.14.14.1
• Gene Name: CYP3A43
• UniProt ID: CP343_HUMAN
• EC Number: 1.14.14.1
• Pfam ID: PF00067
• Sequence:
  MDLIPNFAMETWVLVATSLVLLYIYGTHSHKLFKKLGIPGPTPLPFLGTILFYLRGLWNF
  DRECNEKYGEMWGLYEGQQPMLVIMDPDMIKTVLVKECYSVFTNQMPLGPMGFLKSALSF
  AEDEEWKRIRTLLSPAFTSVKFKEMVPIISQCGDMLVRSLRQEAENSKSINLKDFFGAYT
  MDVITGTLFGVNLDSLNNPQDPFLKNMKKLLKLDFLDPFLLLISLFPFLTPVFEALNIGL
  FPKDVTHFLKNSIERMKESRLKDKQKHRVDFFQQMIDSQNSKETKSHKALSDLELVAQSI
  IIIFAAYDTTSTTLPFIMYELATHPDVQQKLQEEIDAVLPNKAPVTYDALVQMEYLDMVV
  NETLRLFPVVSRVTRVCKKDIEINGVFIPKGLAVMVPIYALHHDPKYWTEPEKFCPERFS
  KKNKDSIDLYRYIPFGAGPRNCIGMRFALTNIKLAVIRALQNFSFKPCKETQIPLKLDNL
  PILQPEKPIVLKVHLRDGITSGP
• Function: Exhibits low testosterone 6-beta-hydroxylase activity.
• Tissue Specificity: Highest expression level in prostate. Also expressed in liver, kidney, pancreas, fetal liver and fetal skeletal muscle.
• KEGG Pathway: Chemical carcinogenesis - D. adducts (hsa05204)
• Reactome Pathway:
  Xenobiotics (R-HSA-211981)
  Miscellaneous substrates (R-HSA-211958)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Testosterone	DM7HUNW	Approved	Cytochrome P450 3A43 (CYP3A43) affects the metabolism of Testosterone.	[12]

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 Cytochrome P450 3A43 (CYP3A43).	[1]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cytochrome P450 3A43 (CYP3A43).	[2]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Cytochrome P450 3A43 (CYP3A43).	[3]
Carbamazepine	DMZOLBI	Approved	Carbamazepine increases the expression of Cytochrome P450 3A43 (CYP3A43).	[4]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Cytochrome P450 3A43 (CYP3A43).	[5]
Obeticholic acid	DM3Q1SM	Approved	Obeticholic acid decreases the expression of Cytochrome P450 3A43 (CYP3A43).	[6]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Cytochrome P450 3A43 (CYP3A43).	[7]
Bosentan	DMIOGBU	Approved	Bosentan affects the expression of Cytochrome P450 3A43 (CYP3A43).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Cytochrome P450 3A43 (CYP3A43).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Cytochrome P450 3A43 (CYP3A43).	[11]

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 increases the methylation of Cytochrome P450 3A43 (CYP3A43).	[10]

References

• [1] 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.
• [2] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [3] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [4] Transcriptional profiling of genes induced in the livers of patients treated with carbamazepine. Clin Pharmacol Ther. 2006 Nov;80(5):440-456.
• [5] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [6] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [7] Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
• [8] Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.
• [12] CYP3A4, CYP3A5, and CYP3A43 genotypes and haplotypes in the etiology and severity of prostate cancer. Cancer Res. 2004 Nov 15;64(22):8461-7. doi: 10.1158/0008-5472.CAN-04-1651.