Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA7K5XA)

• DOT Name: Glutathione S-transferase A1 (GSTA1)
• Synonyms: EC 2.5.1.18; 13-hydroperoxyoctadecadienoate peroxidase; EC 1.11.1.-; Androst-5-ene-3,17-dione isomerase; EC 5.3.3.-; GST HA subunit 1; GST class-alpha member 1; GST-epsilon; GSTA1-1; GTH1
• Gene Name: GSTA1
• UniProt ID: GSTA1_HUMAN
• PDB ID: 1GSD ; 1GSE ; 1GSF ; 1GUH ; 1K3L ; 1K3O ; 1K3Y ; 1LBK ; 1PKW ; 1PKZ ; 1PL1 ; 1PL2 ; 1USB ; 1XWG ; 1YDK ; 2R3X ; 2R6K ; 3I69 ; 3I6A ; 3IK9 ; 3KTL ; 3L0H ; 3Q74 ; 3U6V ; 3ZFB ; 3ZFL ; 4HJ2 ; 5JCU ; 5LCZ ; 5LD0 ; 6ATO ; 6ATP ; 6ATQ ; 6ATR ; 6YAW ; 7BIB ; 7BIC ; 8BHC ; 8BHE
• EC Number: 1.11.1.-; 2.5.1.18; 5.3.3.-
• Pfam ID: PF00043 ; PF02798
• Sequence:
  MAEKPKLHYFNARGRMESTRWLLAAAGVEFEEKFIKSAEDLDKLRNDGYLMFQQVPMVEI
  DGMKLVQTRAILNYIASKYNLYGKDIKERALIDMYIEGIADLGEMILLLPVCPPEEKDAK
  LALIKEKIKNRYFPAFEKVLKSHGQDYLVGNKLSRADIHLVELLYYVEELDSSLISSFPL
  LKALKTRISNLPTVKKFLQPGSPRKPPMDEKSLEEARKIFRF
• Function: Glutathione S-transferase that catalyzes the nucleophilic attack of the sulfur atom of glutathione on the electrophilic groups of a wide range of exogenous and endogenous compounds (Probable). Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2). It also catalyzes the isomerization of D5-androstene-3,17-dione (AD) into D4-androstene-3,17-dione and may therefore play an important role in hormone biosynthesis. Through its glutathione-dependent peroxidase activity toward the fatty acid hydroperoxide (13S)-hydroperoxy-(9Z,11E)-octadecadienoate/13-HPODE it is also involved in the metabolism of oxidized linoleic acid.
• Tissue Specificity: Liver.
• KEGG Pathway:
  Glutathione metabolism (hsa00480)
  Metabolism of xenobiotics by cytochrome P450 (hsa00980)
  Drug metabolism - cytochrome P450 (hsa00982)
  Drug metabolism - other enzymes (hsa00983)
  Metabolic pathways (hsa01100)
  Platinum drug resistance (hsa01524)
  Pathways in cancer (hsa05200)
  Chemical carcinogenesis - D. adducts (hsa05204)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Hepatocellular carcinoma (hsa05225)
  Fluid shear stress and atherosclerosis (hsa05418)
• Reactome Pathway:
  Heme degradation (R-HSA-189483)
  Azathioprine ADME (R-HSA-9748787)
  NFE2L2 regulating anti-oxidant/detoxification enzymes (R-HSA-9818027)
  Glutathione conjugation (R-HSA-156590)
• BioCyc Pathway: MetaCyc:G66-32542-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 6 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Glutathione S-transferase A1 (GSTA1) decreases the response to substance of Doxorubicin.	[42]
Cisplatin	DMRHGI9	Approved	Glutathione S-transferase A1 (GSTA1) decreases the response to substance of Cisplatin.	[43]
Clozapine	DMFC71L	Approved	Glutathione S-transferase A1 (GSTA1) decreases the activity of Clozapine.	[46]
Busulfan	DMXYJ9C	Approved	Glutathione S-transferase A1 (GSTA1) decreases the response to substance of Busulfan.	[49]
Ethacrynic acid	DM60QMR	Approved	Glutathione S-transferase A1 (GSTA1) decreases the response to substance of Ethacrynic acid.	[51]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	Glutathione S-transferase A1 (GSTA1) decreases the response to substance of 4-hydroxy-2-nonenal.	[54]

This DOT Affected the Biotransformations of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Progesterone	DMUY35B	Approved	Glutathione S-transferase A1 (GSTA1) increases the chemical synthesis of Progesterone.	[44]
Nevirapine	DM6HX9B	Approved	Glutathione S-transferase A1 (GSTA1) increases the glutathionylation of Nevirapine.	[48]
Mefenamic acid	DMK7HFI	Approved	Glutathione S-transferase A1 (GSTA1) increases the glutathionylation of Mefenamic acid.	[50]
4-ANDROSTENE-3-17-DIONE	DMSE8NU	Investigative	Glutathione S-transferase A1 (GSTA1) increases the chemical synthesis of 4-ANDROSTENE-3-17-DIONE.	[44]

This DOT Affected the Regulation of Drug Effects of 8 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Azathioprine	DMMZSXQ	Approved	Glutathione S-transferase A1 (GSTA1) affects the metabolism of Azathioprine.	[45]
Glutathione	DMAHMT9	Approved	Glutathione S-transferase A1 (GSTA1) affects the metabolism of Glutathione.	[47]
Thiotepa	DMIZKOP	Approved	Glutathione S-transferase A1 (GSTA1) affects the export of Thiotepa.	[52]
DNCB	DMDTVYC	Phase 2	Glutathione S-transferase A1 (GSTA1) increases the metabolism of DNCB.	[53]
PGJ2	DMR2LTC	Investigative	Glutathione S-transferase A1 (GSTA1) affects the metabolism of PGJ2.	[55]
TEPA (possesses cytotoxic activity)	DMROS5K	Investigative	Glutathione S-transferase A1 (GSTA1) affects the export of TEPA (possesses cytotoxic activity).	[52]
Prostaglandin A2	DMWC4X8	Investigative	Glutathione S-transferase A1 (GSTA1) affects the metabolism of Prostaglandin A2.	[55]
CTK1G9578	DMI3J0F	Investigative	Glutathione S-transferase A1 (GSTA1) increases the metabolism of CTK1G9578.	[56]

44 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 Glutathione S-transferase A1 (GSTA1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Glutathione S-transferase A1 (GSTA1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Glutathione S-transferase A1 (GSTA1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Glutathione S-transferase A1 (GSTA1).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Glutathione S-transferase A1 (GSTA1).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Glutathione S-transferase A1 (GSTA1).	[6]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Glutathione S-transferase A1 (GSTA1).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Glutathione S-transferase A1 (GSTA1).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine increases the expression of Glutathione S-transferase A1 (GSTA1).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Glutathione S-transferase A1 (GSTA1).	[10]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Glutathione S-transferase A1 (GSTA1).	[11]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Glutathione S-transferase A1 (GSTA1).	[8]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Glutathione S-transferase A1 (GSTA1).	[12]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the activity of Glutathione S-transferase A1 (GSTA1).	[13]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of Glutathione S-transferase A1 (GSTA1).	[14]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Glutathione S-transferase A1 (GSTA1).	[15]
Phenytoin	DMNOKBV	Approved	Phenytoin increases the expression of Glutathione S-transferase A1 (GSTA1).	[16]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone increases the expression of Glutathione S-transferase A1 (GSTA1).	[17]
Nefazodone	DM4ZS8M	Approved	Nefazodone decreases the expression of Glutathione S-transferase A1 (GSTA1).	[18]
Dopamine	DMPGUCF	Approved	Dopamine decreases the activity of Glutathione S-transferase A1 (GSTA1).	[19]
Atazanavir	DMSYRBX	Approved	Atazanavir decreases the expression of Glutathione S-transferase A1 (GSTA1).	[18]
Chlorambucil	DMRKE63	Approved	Chlorambucil decreases the activity of Glutathione S-transferase A1 (GSTA1).	[20]
Benzoic acid	DMKB9FI	Approved	Benzoic acid increases the activity of Glutathione S-transferase A1 (GSTA1).	[21]
Artemisinin	DMOY7W3	Approved	Artemisinin decreases the activity of Glutathione S-transferase A1 (GSTA1).	[22]
Methyldopa	DM5I621	Approved	Methyldopa decreases the activity of Glutathione S-transferase A1 (GSTA1).	[19]
Rifamycin	DMEH3O7	Approved	Rifamycin increases the expression of Glutathione S-transferase A1 (GSTA1).	[23]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Glutathione S-transferase A1 (GSTA1).	[24]
Bardoxolone methyl	DMODA2X	Phase 3	Bardoxolone methyl decreases the expression of Glutathione S-transferase A1 (GSTA1).	[25]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Glutathione S-transferase A1 (GSTA1).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Glutathione S-transferase A1 (GSTA1).	[27]
Eugenol	DM7US1H	Patented	Eugenol decreases the activity of Glutathione S-transferase A1 (GSTA1).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Glutathione S-transferase A1 (GSTA1).	[29]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Glutathione S-transferase A1 (GSTA1).	[30]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE decreases the expression of Glutathione S-transferase A1 (GSTA1).	[31]
Okadaic acid	DM47CO1	Investigative	Okadaic acid decreases the expression of Glutathione S-transferase A1 (GSTA1).	[32]
Chlorpyrifos	DMKPUI6	Investigative	Chlorpyrifos increases the expression of Glutathione S-transferase A1 (GSTA1).	[33]
Bilirubin	DMI0V4O	Investigative	Bilirubin increases the expression of Glutathione S-transferase A1 (GSTA1).	[34]
Lead acetate	DML0GZ2	Investigative	Lead acetate increases the expression of Glutathione S-transferase A1 (GSTA1).	[35]
Kaempferol	DMHEMUB	Investigative	Kaempferol increases the expression of Glutathione S-transferase A1 (GSTA1).	[36]
GW7647	DM9RD0C	Investigative	GW7647 decreases the expression of Glutathione S-transferase A1 (GSTA1).	[37]
Linoleic acid	DMDGPY9	Investigative	Linoleic acid increases the expression of Glutathione S-transferase A1 (GSTA1).	[38]
USNIC ACID	DMGOURX	Investigative	USNIC ACID increases the expression of Glutathione S-transferase A1 (GSTA1).	[39]
Alpha-linolenic acid	DMY64HE	Investigative	Alpha-linolenic acid increases the expression of Glutathione S-transferase A1 (GSTA1).	[38]
3-Methylpyridine	DMF3JHM	Investigative	3-Methylpyridine decreases the expression of Glutathione S-transferase A1 (GSTA1).	[23]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
1-anilinonaphthalene-8-sulfonic acid	DMNGY0E	Investigative	1-anilinonaphthalene-8-sulfonic acid affects the binding of Glutathione S-transferase A1 (GSTA1).	[40]
S-hexylglutathione	DMNWP02	Investigative	S-hexylglutathione affects the binding of Glutathione S-transferase A1 (GSTA1).	[41]

References

• [1] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [2] 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.
• [3] Acetaminophen-induced hepatocyte injury: C2-ceramide and oltipraz intervention, hepatocyte nuclear factor 1 and glutathione S-transferase A1 changes. J Appl Toxicol. 2019 Dec;39(12):1640-1650. doi: 10.1002/jat.3881. Epub 2019 Aug 6.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [6] 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.
• [7] Atrazine potentiation of arsenic trioxide-induced cytotoxicity and gene expression in human liver carcinoma cells (HepG2). Mol Cell Biochem. 2001 Jun;222(1-2):49-59.
• [8] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] Transcriptional profiling of genes induced in the livers of patients treated with carbamazepine. Clin Pharmacol Ther. 2006 Nov;80(5):440-456.
• [10] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [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] Dexamethasone induces human glutathione S transferase alpha 1 (hGSTA1) expression through the activation of glucocorticoid receptor (hGR). Toxicology. 2017 Jun 15;385:59-66.
• [13] Simulation of interindividual differences in inactivation of reactive para-benzoquinone imine metabolites of diclofenac by glutathione S-transferases in human liver cytosol. Toxicol Lett. 2016 Jul 25;255:52-62.
• [14] Ketoconazole and miconazole are antagonists of the human glucocorticoid receptor: consequences on the expression and function of the constitutive androstane receptor and the pregnane X receptor. Mol Pharmacol. 2006 Jul;70(1):329-39.
• [15] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [16] Effects of phenytoin on glutathione status and oxidative stress biomarker gene mRNA levels in cultured precision human liver slices. Toxicol Sci. 2001 Jan;59(1):118-26.
• [17] Overexpression of glutathione-S-transferase A1 in benign adrenocortical adenomas from patients with Cushing's syndrome. J Clin Endocrinol Metab. 2001 Apr;86(4):1653-9.
• [18] 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.
• [19] Inhibition of human glutathione S-transferases by dopamine, alpha-methyldopa and their 5-S-glutathionyl conjugates. Chem Biol Interact. 1994 Jan;90(1):87-99.
• [20] Role of multidrug resistance protein 1 (MRP1) and glutathione S-transferase A1-1 in alkylating agent resistanceKinetics of glutathione conjugate formation and efflux govern differential cellular sensitivity to chlorambucil versus melphalan toxicity. J Biol Chem. 2001 Mar 16;276(11):7952-6.
• [21] Benzoic acid derivatives induce recovery of catalytic activity in the partially inactive Met208Lys mutant of human glutathione transferase A1-1. J Mol Biol. 1999 May 14;288(4):787-800.
• [22] Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. Int J Cancer. 2002 Feb 10;97(5):700-5.
• [23] The influence of picolines on glutathione transferase activity and subunit composition in human liver derived Hep G2 cells. Biochem Pharmacol. 1994 Nov 16;48(10):1976-8.
• [24] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [25] Fluorescent tagging of endogenous Heme oxygenase-1 in human induced pluripotent stem cells for high content imaging of oxidative stress in various differentiated lineages. Arch Toxicol. 2021 Oct;95(10):3285-3302. doi: 10.1007/s00204-021-03127-8. Epub 2021 Sep 4.
• [26] Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells. PLoS One. 2022 Apr 29;17(4):e0266966. doi: 10.1371/journal.pone.0266966. eCollection 2022.
• [27] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [28] Inhibition of rat, mouse, and human glutathione S-transferase by eugenol and its oxidation products. Chem Biol Interact. 1996 Jan 5;99(1-3):85-97.
• [29] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [30] Sulforaphane and quercetin modulate PhIP-DNA adduct formation in human HepG2 cells and hepatocytes. Carcinogenesis. 2003 Dec;24(12):1903-11.
• [31] Protective effects of xanthohumol against the genotoxicity of heterocyclic aromatic amines MeIQx and PhIP in bacteria and in human hepatoma (HepG2) cells. Food Chem Toxicol. 2012 Mar;50(3-4):949-55.
• [32] Whole genome mRNA transcriptomics analysis reveals different modes of action of the diarrheic shellfish poisons okadaic acid and dinophysis toxin-1 versus azaspiracid-1 in Caco-2 cells. Toxicol In Vitro. 2018 Feb;46:102-112.
• [33] Organophosphate pesticides increase the expression of alpha glutathione S-transferase in HepG2 cells. Toxicol In Vitro. 2011 Dec;25(8):2074-9.
• [34] Interleukin 1beta inhibits CAR-induced expression of hepatic genes involved in drug and bilirubin clearance. Hepatology. 2004 Oct;40(4):951-60.
• [35] The role of Nrf2 in protection against Pb-induced oxidative stress and apoptosis in SH-SY5Y cells. Food Chem Toxicol. 2015 Dec;86:191-201.
• [36] Single and concerted effects of benzo[a]pyrene and flavonoids on the AhR and Nrf2-pathway in the human colon carcinoma cell line Caco-2. Toxicol In Vitro. 2011 Apr;25(3):671-83.
• [37] Identifying qualitative differences in PPAR signaling networks in human and rat hepatocytes and their significance for next generation chemical risk assessment methods. Toxicol In Vitro. 2020 Apr;64:104463. doi: 10.1016/j.tiv.2019.02.017. Epub 2019 Oct 15.
• [38] High fat diet-induced hepatic 18-carbon fatty acids accumulation up-regulates CYP2A5/CYP2A6 via NF-E2-related factor 2. Front Pharmacol. 2017 May 15;8:233.
• [39] Activation of the Nrf2 signaling pathway in usnic acid-induced toxicity in HepG2 cells. Arch Toxicol. 2017 Mar;91(3):1293-1307.
• [40] Residue 219 impacts on the dynamics of the C-terminal region in glutathione transferase A1-1: implications for stability and catalytic and ligandin functions. Biochemistry. 2003 Dec 30;42(51):15326-32. doi: 10.1021/bi035671z.
• [41] 1.3-A resolution structure of human glutathione S-transferase with S-hexyl glutathione bound reveals possible extended ligandin binding site. Proteins. 2002 Sep 1;48(4):618-27. doi: 10.1002/prot.10162.
• [42] Glutathione S-transferases as antioxidant enzymes: small cell lung cancer (H69) cells transfected with hGSTA1 resist doxorubicin-induced apoptosis. Arch Biochem Biophys. 2006 Aug 15;452(2):165-73. doi: 10.1016/j.abb.2006.04.006. Epub 2006 May 5.
• [43] Establishment of cisplatin-resistant ovarian yolk sac tumor cells and investigation of the mechanism of cisplatin resistance using this cell line. Gynecol Obstet Invest. 2011;71(2):104-11. doi: 10.1159/000320744. Epub 2010 Dec 9.
• [44] Human glutathione S-transferase A (GSTA) family genes are regulated by steroidogenic factor 1 (SF-1) and are involved in steroidogenesis. FASEB J. 2013 Aug;27(8):3198-208. doi: 10.1096/fj.12-222745. Epub 2013 May 6.
• [45] Structural determinants of glutathione transferases with azathioprine activity identified by DNA shuffling of alpha class members. J Mol Biol. 2008 Feb 1;375(5):1365-79. doi: 10.1016/j.jmb.2007.11.034. Epub 2007 Nov 19.
• [46] Role of human glutathione S-transferases in the inactivation of reactive metabolites of clozapine. Chem Res Toxicol. 2010 Sep 20;23(9):1467-76. doi: 10.1021/tx100131f.
• [47] Busulfan conjugation by glutathione S-transferases alpha, mu, and pi. Drug Metab Dispos. 1996 Sep;24(9):1015-9.
• [48] Different Reactive Metabolites of Nevirapine Require Distinct Glutathione S-Transferase Isoforms for Bioinactivation. Chem Res Toxicol. 2016 Dec 19;29(12):2136-2144. doi: 10.1021/acs.chemrestox.6b00250. Epub 2016 Nov 28.
• [49] Overexpression of glutathione S-transferase A1-1 in ECV 304 cells protects against busulfan mediated G2-arrest and induces tissue factor expression. Br J Pharmacol. 2002 Dec;137(7):1100-6. doi: 10.1038/sj.bjp.0704972.
• [50] Cytochrome P450-mediated bioactivation of mefenamic acid to quinoneimine intermediates and inactivation by human glutathione S-transferases. Chem Res Toxicol. 2014 Dec 15;27(12):2071-81.
• [51] Antineoplastic drug sensitivity of human MCF-7 breast cancer cells stably transfected with a human alpha class glutathione S-transferase gene. Cancer Res. 1991 Jan 15;51(2):587-94.
• [52] Polymorphisms of drug-metabolizing enzymes (GST, CYP2B6 and CYP3A) affect the pharmacokinetics of thiotepa and tepa. Br J Clin Pharmacol. 2009 Jan;67(1):50-60. doi: 10.1111/j.1365-2125.2008.03321.x. Epub 2008 Nov 17.
• [53] Human glutathione S-transferases. The Ha multigene family encodes products of different but overlapping substrate specificities. J Biol Chem. 1988 Sep 15;263(26):12797-800.
• [54] Genotoxicity of 4-hydroxy-2-nonenal in human colon tumor cells is associated with cellular levels of glutathione and the modulation of glutathione S-transferase A4 expression by butyrate. Toxicol Sci. 2005 Jul;86(1):27-35. doi: 10.1093/toxsci/kfi171. Epub 2005 Apr 13.
• [55] Stereoselective conjugation of prostaglandin A2 and prostaglandin J2 with glutathione, catalyzed by the human glutathione S-transferases A1-1, A2-2, M1a-1a, and P1-1. Chem Res Toxicol. 1997 Mar;10(3):310-7. doi: 10.1021/tx9601770.
• [56] Genetic analysis of glutathione S-transferase A1 polymorphism in the Chinese population and the influence of genotype on enzymatic properties. Toxicol Sci. 2006 Feb;89(2):438-43. doi: 10.1093/toxsci/kfj037. Epub 2005 Nov 9.