GPA512

GPA512 is an orally active STAT3 inhibitor and a prodrug of Galiellalactone (HY-125170). GPA512 inhibits the binding of STAT3 to DNA, downregulates STAT3-activated genes, and suppresses tumor growth in prostate cancer xenograft models. GPA512 is rapidly converted to Galiellalactone in plasma. GPA512 can be used in research related to castration-resistant prostate cancer^[1][2]. In Vitro:GPA512 is rapidly converted into its active metabolite Galiellalactone (HY-125170) in plasma across species at 37°C^[1][2].
GPA512 (5 μM; monitored over 0-120 min) exhibits moderate symmetric permeability across Caco-2 cell monolayers, with no directional preference between absorptive and secretive transport^[2].
GPA512 (10 μM; 2 h) is completely metabolized by mouse hepatocytes within 2 h, primarily via ester hydrolysis to form carboxylic acid (compound 3), which then spontaneously converts to Galiellalactone^[2].
GPA512 (compound 6) inhibits the proliferation of human prostate cancer cell line DU145 after 72 h, with an IC₅₀ value of 4.81 μM^[2]. In Vivo:GPA512 (compound 6) (40 mg/kg; p.o.; daily five times per week; 28 days) significantly inhibits DU145 prostate cancer xenograft growth in NMRI-nude mice by reducing tumor cell proliferation and increasing apoptosis via STAT3 pathway inhibition, with no observed toxicity^[1][2].
GPA512 (40-400 mg/kg; p.o.; single dose) is well tolerated in male CD1 mice, with no observed toxicity^[2].