Details of the Drug

General Information of Drug (ID: DMAHMT9)

Drug Name
Glutathione
Synonyms
glutathione; 70-18-8; Glutathion; Isethion; Tathion; Glutathione-SH; Glutinal; reduced glutathione; Neuthion; Deltathione; Copren; L-Glutathione reduced; Glutide; Tathione; Triptide; Ledac; Glutatione; GSH; Glutatiol; Panaron; gamma-L-Glutamyl-L-cysteinylglycine; Glutathione SH; L-Glutatione; Glutathione (reduced); Agifutol S; L-gamma-glutamyl-L-cysteinylglycine; gamma-L-glutamyl-L-cysteinyl-glycine; 5-L-Glutamyl-L-cysteinylglycine; Glutathione [JAN]; glutathione red; gamma-L-Glutamylcysteinylglycine; red. glutathione
Indication
Disease Entry ICD 11 Status REF
Human immunodeficiency virus infection 1C62 Approved [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 2 Molecular Weight (mw) 307.33
Logarithm of the Partition Coefficient (xlogp) -4.5
Rotatable Bond Count (rotbonds) 9
Hydrogen Bond Donor Count (hbonddonor) 6
Hydrogen Bond Acceptor Count (hbondacc) 8
Chemical Identifiers
Formula
C10H17N3O6S
IUPAC Name
(2S)-2-amino-5-[[(2R)-1-(carboxymethylamino)-1-oxo-3-sulfanylpropan-2-yl]amino]-5-oxopentanoic acid
Canonical SMILES
C(CC(=O)N[C@@H](CS)C(=O)NCC(=O)O)[C@@H](C(=O)O)N
InChI
InChI=1S/C10H17N3O6S/c11-5(10(18)19)1-2-7(14)13-6(4-20)9(17)12-3-8(15)16/h5-6,20H,1-4,11H2,(H,12,17)(H,13,14)(H,15,16)(H,18,19)/t5-,6-/m0/s1
InChIKey
RWSXRVCMGQZWBV-WDSKDSINSA-N
Cross-matching ID
PubChem CID
124886
ChEBI ID
CHEBI:16856
CAS Number
70-18-8
DrugBank ID
DB00143
TTD ID
D02HFD
VARIDT ID
DR00039
INTEDE ID
DR2036

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Enzyme unspecific (Enz) TT3C1VN NOUNIPROTAC Modulator [2]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [3]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [4]
Multidrug resistance-associated protein 1 (ABCC1) DTSYQGK MRP1_HUMAN Substrate [5]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [6]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [7]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Glutathione S-transferase omega-2 (GSTO2) DEHMPZR GSTO2_HUMAN Substrate [9]
Glutathione S-transferase omega-1 (GSTO1) DEZSNJD GSTO1_HUMAN Substrate [9]
Glutathione peroxidase 6 (GPX6) DEOS3FD GPX6_HUMAN Substrate [10]
Gamma-glutamyltranspeptidase 5 (GGT5) DEH6CAO GGT5_HUMAN Substrate [11]
Gamma-glutamylcyclotransferase (GGCT) DEKW6PB A0A073ACX1_RALSL Substrate [12], [13]
Gamma-glutamylcyclotransferase 2 (CHAC2) DEB4JZV CHAC2_HUMAN Substrate [14]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Protein Interaction/Cellular Processes [15]
Aldo-keto reductase family 1 member B1 (AKR1B1) OTRX72TH ALDR_HUMAN Post-Translational Modifications [16]
Alpha-synuclein (SNCA) OTPWC1MR SYUA_HUMAN Regulation of Drug Effects [17]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Gene/Protein Processing [18]
Arsenite methyltransferase (AS3MT) OTNLWD0N AS3MT_HUMAN Protein Interaction/Cellular Processes [19]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Regulation of Drug Effects [20]
ATP-binding cassette sub-family C member 4 (ABCC4) OTO27PAL MRP4_HUMAN Regulation of Drug Effects [20]
ATP-binding cassette sub-family C member 5 (ABCC5) OT34G4US MRP5_HUMAN Regulation of Drug Effects [20]
C-C motif chemokine 20 (CCL20) OTUCJY4N CCL20_HUMAN Gene/Protein Processing [21]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Gene/Protein Processing [18]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6737).
2 Methionine and cysteine affect glutathione level, glutathione-related enzyme activities and the expression of glutathione S-transferase isozymes in rat hepatocytes. J Nutr. 1997 Nov;127(11):2135-41.
3 Oxidative and electrophilic stress induces multidrug resistance-associated protein transporters via the nuclear factor-E2-related factor-2 transcriptional pathway. Hepatology. 2007 Nov;46(5):1597-610.
4 Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues. Biochem J. 2002 Feb 1;361(Pt 3):497-503.
5 Structural determinants of substrate specificity differences between human multidrug resistance protein (MRP) 1 (ABCC1) and MRP3 (ABCC3). Drug Metab Dispos. 2008 Dec;36(12):2571-81.
6 Glutathione transport is a unique function of the ATP-binding cassette protein ABCG2. J Biol Chem. 2010 May 28;285(22):16582-7.
7 Regulation of Organic Anion Transporting Polypeptides (OATP) 1B1- and OATP1B3-Mediated Transport: An Updated Review in the Context of OATP-Mediated Drug-Drug Interactions. Int J Mol Sci. 2018 Mar 14;19(3). pii: E855.
8 Upregulation of cellular glutathione levels in human ABCB5- and murine Abcb5-transfected cells. BMC Pharmacol Toxicol. 2015 Dec 15;16:37.
9 Structural insights into the dehydroascorbate reductase activity of human omega-class glutathione transferases. J Mol Biol. 2012 Jul 13;420(3):190-203.
10 Metabolomics reveals a role for the chromatin-binding protein HMGN5 in glutathione metabolism. PLoS One. 2014 Jan 2;9(1):e84583.
11 Gamma-glutamyl compounds: substrate specificity of gamma-glutamyl transpeptidase enzymes. Anal Biochem. 2011 Jul 15;414(2):208-14.
12 Characterization of the mechanism of thioredoxin-dependent activation of gamma-glutamylcyclotransferase, RipAY, from Ralstonia solanacearum. Biochem Biophys Res Commun. 2020 Mar 12;523(3):759-765.
13 Vaginal microbiome in early pregnancy and subsequent risk of spontaneous preterm birth: a case-control study. BJOG. 2019 Feb;126(3):349-358.
14 ChaC2, an enzyme for slow turnover of cytosolic glutathione. J Biol Chem. 2017 Jan 13;292(2):638-651.
15 A low molecular weight copper chelator crosses the blood-brain barrier and attenuates experimental autoimmune encephalomyelitis. J Neurochem. 2004 Jun;89(5):1241-51. doi: 10.1111/j.1471-4159.2004.02428.x.
16 Posttranslational glutathiolation of aldose reductase (AKR1B1): a possible mechanism of protein recovery from S-nitrosylation. Chem Biol Interact. 2009 Mar 16;178(1-3):250-8. doi: 10.1016/j.cbi.2008.11.007. Epub 2008 Nov 18.
17 Protective effect of Geraniol on the transgenic Drosophila model of Parkinson's disease. Environ Toxicol Pharmacol. 2016 Apr;43:225-31. doi: 10.1016/j.etap.2016.03.018. Epub 2016 Mar 22.
18 Apoptosis induced by extracellular glutathione is mediated by H(2)O(2) production and DNA damage. Int J Cancer. 2000 Aug 1;87(3):343-8. doi: 10.1002/1097-0215(20000801)87:3<343::aid-ijc6>3.0.co;2-8.
19 Rapid equilibrium kinetic analysis of arsenite methylation catalyzed by recombinant human arsenic (+3 oxidation state) methyltransferase (hAS3MT). J Biol Chem. 2012 Nov 9;287(46):38790-9. doi: 10.1074/jbc.M112.368050. Epub 2012 Sep 6.
20 Selenium-dependent and -independent transport of arsenic by the human multidrug resistance protein 2 (MRP2/ABCC2): implications for the mutual detoxification of arsenic and selenium. Carcinogenesis. 2010 Aug;31(8):1450-5. doi: 10.1093/carcin/bgq125. Epub 2010 Jun 27.
21 Mechanical stress-activated immune response genes via Sirtuin 1 expression in human periodontal ligament cells. Clin Exp Immunol. 2012 Apr;168(1):113-24. doi: 10.1111/j.1365-2249.2011.04549.x.