Glutathione S-transferase P (GSTP1) (GSTP1)

Glutathione S-transferase P (GSTP1) is a key Phase II detoxification enzyme that catalyzes the conjugation of reduced glutathione (GSH) to a wide variety of exogenous and endogenous electrophilic compounds (Source: UniProt P09211). The functional enzyme exists as a homodimer (GSTP1-1) and features a highly conserved catalytic G-site for glutathione binding and a more variable H-site for hydrophobic substrates (Source: PubMed 15170586). In addition to its enzymatic activity, GSTP1 serves as a non-enzymatic regulator of the Mitogen-Activated Protein Kinase (MAPK) pathway by binding to and inhibiting c-Jun N-terminal kinase (JNK), thereby suppressing apoptosis (Source: PubMed 10417334). GSTP1 is frequently overexpressed in various human cancers, where it contributes to chemotherapy resistance by detoxifying drugs and preventing stress-induced cell death (Source: PubMed 25403157). Therapeutic approaches targeting GSTP1 include small-molecule inhibitors like Ezatiostat to sensitize tumors to chemotherapy and prodrugs like Canfosfamide that are specifically activated by the enzyme's catalytic activity within cancer cells (Source: PubChem CID 115149).

Other names

GSTP1-1Glutathione S-transferase pi 1GST class-piGST3FAEES3Glutathione S-transferase P1-1GSTP1-1 – catalytic G-site

GSTP1-targeted therapies primarily utilize three mechanisms: direct inhibition of the catalytic G-site or H-site to block the detoxification of co-administered chemotherapeutic agents; the use of GSTP1-activated prodrugs (e.g., Canfosfamide) that release cytotoxic moieties upon conjugation; and the disruption of the GSTP1-JNK protein-protein interaction to re-enable stress-induced apoptosis in malignant cells (Source: PubMed 25403157, 15170586).