GSTO1-IN-1

GSTO1-IN-1 is a potent glutathione S-transferase omega 1 (GSTO1) inhibitor with an IC₅₀ of 31 nM. IC50 & Target: IC50: 31 nM (GSTO1)^[1] In Vitro: GSTO1-IN-1 (C1-27) potently inhibits GSTO1 enzyme activity with an IC₅₀ value of 31 nM. GSTO1-IN-1 also potently competes with 5-chloromethylfluorescein diacetate (CMFDA) for binding to recombinant protein, as well as endogenous GSTO1 in the milieu of a soluble proteome. HCT116 cells treated with GSTO1-IN-1 also show a decrease in cell viability in a dose-dependent manner. GSTO1-IN-1 inhibits the clonogenic survival of HCT116 cells at sub-micromolar concentrations^[1]. In Vivo: To test whether GSTO1-IN-1 had in vivo efficacy, its effects are evaluated in a human colon cancer cell line xenograft model. GSTO1-IN-1 (20-45 mg/kg) is administered as a single agent to nude mice bearing HCT116 xenografts. After 5 weeks of treatment, tumor growth is significantly inhibited in GSTO1-IN-1-treated mice compared with the vehicle-treated group (P<0.05). GSTO1-IN-1 treatment is generally well tolerated by mice up to 45 mg/kg, with no overt signs of toxicity and no significant variations in average body weights throughout the duration of the study^[1].