Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT40K12)

• DTT Name: Glutathione S-transferase P (GSTP1)
• Synonyms: GSTP11; GSTP1-1; GST3; GST classpi; GST class-pi; FAEES3
• Gene Name: GSTP1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Alkyl aryl transferase
• UniProt ID: GSTP1_HUMAN
• TTD ID: T21669
• EC Number: EC 2.5.1.18
• Sequence:
  MPPYTVVYFPVRGRCAALRMLLADQGQSWKEEVVTVETWQEGSLKASCLYGQLPKFQDGD
  LTLYQSNTILRHLGRTLGLYGKDQQEAALVDMVNDGVEDLRCKYISLIYTNYEAGKDDYV
  KALPGQLKPFETLLSQNQGGKTFIVGDQISFADYNLLDLLLIHEVLAPGCLDAFPLLSAY
  VGRLSARPKLKAFLASPEYVNLPINGNGKQ
• Function: Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration. Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
• KEGG Pathway:
  Glutathione metabolism (hsa00480)
  Metabolism of xenobiotics by cytochrome P450 (hsa00980)
  Drug metabolism - cytochrome P450 (hsa00982)
  Pathways in cancer (hsa05200)
  Chemical carcinogenesis (hsa05204)
  Prostate cancer (hsa05215)
• Reactome Pathway:
  Detoxification of Reactive Oxygen Species (R-HSA-3299685)
  Neutrophil degranulation (R-HSA-6798695)
  Paracetamol ADME (R-HSA-9753281)
  Glutathione conjugation (R-HSA-156590)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Canfosfamide	DM4FHQR	Solid tumour/cancer	2A00-2F9Z	Phase 3	[1]
Ezatiostat	DM2L9CO	Myelodysplastic syndrome	2A37	Phase 2	[2]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Myelodysplastic syndrome	2C82	Bone marrow	4.46E-01	1.42E-02	0.03

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Glutathione S-transferase pi (GSTP1) DME Info
• Gene Name: GSTP1

6 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Busulfan	DMXYJ9C	Chronic myelogenous leukaemia	2A20.0	Approved	[3]
Carboplatin	DMG281S	Adenocarcinoma	2D40	Approved	[4]
Chlorambucil	DMRKE63	Chronic lymphocytic leukaemia	2A82.0	Approved	[5]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[6]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[7]
Oxaliplatin	DMQNWRD	Adenocarcinoma	2D40	Approved	[4]

References

• [1] Mechanism of glutathione transferase P1-1-catalyzed activation of the prodrug canfosfamide (TLK286, TELCYTA). Biochemistry. 2013 Nov 12;52(45):8069-78.
• [2] National Cancer Institute Drug Dictionary (drug id 485244).
• [3] Busulfan conjugation by glutathione S-transferases alpha, mu, and pi. Drug Metab Dispos. 1996 Sep;24(9):1015-9.
• [4] PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA150642262)
• [5] The anti-cancer drug chlorambucil as a substrate for the human polymorphic enzyme glutathione transferase P1-1: kinetic properties and crystallographic characterisation of allelic variants. J Mol Biol. 2008 Jun 27;380(1):131-44.
• [6] Glutathione S-transferase genetic polymorphisms and individual sensitivity to the ototoxic effect of cisplatin. Anticancer Drugs. 2000 Sep;11(8):639-43.
• [7] Reactions of glutathione with the catechol, the ortho-quinone and the semi-quinone free radical of etoposide. Consequences for DNA inactivation. Biochem Pharmacol. 1992 Apr 15;43(8):1761-8.