Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMNWP02)

• Drug Name: S-hexylglutathione Drug Info

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 97536
  ChEBI ID: CHEBI:27704
  CAS Number: CAS 24425-56-7
  TTD Drug ID: DMNWP02

Molecule-Related Drug Atlas

Drug(s) Targeting Glutathione-dependent PGD synthase (HPGDS)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Praziquantel	DMOU1PK	Flatworm infection	1F70-1F86	Approved	[4]
HF-0220	DMI4C90	Alzheimer disease	8A20	Phase 2	[5]
Formic Acid	DMNFZC6	Discovery agent	N.A.	Investigative	[6]
Protoporphyrin IX	DMWYE7A	Discovery agent	N.A.	Investigative	[7]
Cibacron blue	DMWE1N8	Discovery agent	N.A.	Investigative	[8]
HQL-79	DMSHYQ3	Discovery agent	N.A.	Investigative	[9]

Drug(s) Affected By Glutathione S-transferase A1 (GSTA1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Artemisinin	DMOY7W3	Malaria	1F40-1F45	Approved	[10]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[11]
Thiotepa	DMIZKOP	Breast cancer	2C60-2C65	Approved	[12]
Phenytoin	DMNOKBV	Epilepsy	8A60-8A68	Approved	[13]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[14]
Ethacrynic acid	DM60QMR	Edema	MG29	Approved	[15]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[16]
Busulfan	DMXYJ9C	Chronic myelogenous leukaemia	2A20.0	Approved	[17]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[18]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[19]

Drug(s) Affected By Glutathione S-transferase Mu 2 (GSTM2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[20]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[21]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[22]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[22]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[23]
Temozolomide	DMKECZD	Adenocarcinoma	2D40	Approved	[24]
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Hypertriglyceridemia	5C80.1	Approved	[25]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[26]
Decitabine	DMQL8XJ	Acute myelogenous leukaemia	2A41	Approved	[27]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[28]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Glutathione-dependent PGD synthase (HPGDS)	TTCYE56	HPGDS_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Glutathione S-transferase A1 (GSTA1)	OTA7K5XA	GSTA1_HUMAN	Protein Interaction/Cellular Processes	[2]
Glutathione S-transferase Mu 2 (GSTM2)	OTG4WT05	GSTM2_HUMAN	Gene/Protein Processing	[3]

References

• [1] Purification and catalytic properties of glutathione transferase from the hepatopancreas of crayfish macrobrachium vollenhovenii (herklots). J Biochem Mol Toxicol. 2004;18(6):332-44.
• [2] 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.
• [3] Ligand-induced changes in the structure and dynamics of a human class Mu glutathione S-transferase. Biochemistry. 2000 Jun 27;39(25):7343-56. doi: 10.1021/bi992767d.
• [4] X-ray structure of glutathione S-transferase from Schistosoma japonicum in a new crystal form reveals flexibility of the substrate-binding site. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Mar 1;61(Pt 3):263-5.
• [5] US patent application no. 2009,0062,529, Multi-cyclic compounds.
• [6] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [7] Inhibition of glutathione-S-transferase from Plasmodium yoelii by protoporphyrin IX, cibacron blue and menadione: implications and therapeutic bene... Parasitol Res. 2008 Mar;102(4):805-7.
• [8] A novel method for screening the glutathione transferase inhibitors. BMC Biochem. 2009 Mar 16;10:6.
• [9] Structural and functional characterization of HQL-79, an orally selective inhibitor of human hematopoietic prostaglandin D synthase. J Biol Chem. 2006 Jun 2;281(22):15277-86.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [20] Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
• [21] 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.
• [22] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [23] 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.
• [24] 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.
• [25] Astaxanthin and omega-3 fatty acids individually and in combination protect against oxidative stress via the Nrf2-ARE pathway. Food Chem Toxicol. 2013 Dec;62:869-75.
• [26] 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.
• [27] Expression of glutathione S-transferase M2 in stage I/II non-small cell lung cancer and alleviation of DNA damage exposure to benzo[a]pyrene. Toxicol Lett. 2010 Feb 15;192(3):316-23. doi: 10.1016/j.toxlet.2009.11.003. Epub 2009 Nov 10.
• [28] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.