GSTO1-IN-1

Description: GSTO1-IN-1, a chloroacetamide-containing compound, is a novel and potent glutathione S-transferase omega 1 (GSTO1) inhibitor with an IC50 of 31 nM. Glutathione S-transferase omega 1 (GSTO1) is an atypical GST isoform that is overexpressed in several cancers and has been implicated in drug resistance. Currently, no small-molecule drug targeting GSTO1 is under clinical development. Co-crystal structures of GSTO1 with GSTO1-IN-1 demonstrate covalent binding to the active site cysteine. These potent GSTO1 inhibitor GSTO1-IN-1 suppresses cancer cell growth, enhance the cytotoxic effects of cisplatin and inhibit tumour growth in colon cancer models as single agent. Bru-seq-based transcription profiling unravelled novel roles for GSTO1 in cholesterol metabolism, oxidative and endoplasmic stress responses, cytoskeleton and cell migration.These findings demonstrate the therapeutic utility of GSTO1 inhibitors as anticancer agents and identify the novel cellular pathways under GSTO1 regulation in colorectal cancer.

References: Nat Commun. 2016 Oct 5; 7:13084.