Y06137

Y06137 is a potent and selective BET inhibitor, which binds to the BRD4(1) bromodomain with a Kd of 81 nM[1]. Antitumor activity[1].

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> Epigenetic Reader Domain

BRD4(1):81 nM (Kd)

Y06137 (0.001-100 nM, 96 hours for LNCaP, C4-2B, and 22Rv1 cells; 144 hours for VCaP cells) exhibits low micromolar or nanomolar potencies (IC50: 0.29-2.6 μΜ) in the four androgen receptor (AR)-positive prostate cancer cell lines LNCaP, C4-2B, 22Rv1, and VCaP. Treatment of 22Rv1 cells with Y06137 (1, 2, 4, 8, and 16 μM, 48 hours) results in significant down-regulation of both full-length (AR-fl) and AR variants levels[1]. Cell Viability Assay[1] Cell Line: LNCaP, C4-2B, 22Rv1, and VCaP prostate cancer cells Concentration: 0.001-100 μM Incubation Time: 96 hours for LNCaP, C4-2B, and 22Rv1; 144 hours for VCaP Result: Inhibited LNCaP, C4-2B, 22Rv1, and VCaP cells with IC50s of 0.47, 0.84, 0.70, 0.29 μM, respectively. Western Blot Analysis[1] Cell Line: 22Rv1 cells Concentration: 1, 2, 4, 8, and 16 μM Incubation Time: 48 hours Result: Resulted in significant down-regulation of both AR-fl and AR variants levels.

Y06137 (50 mg/kg, i.p. injection, 5 times per week, 25 days) demonstrates therapeutic effects in a C4-2B CRPC xenograft tumor model in mice. Y06137 is well tolerated in the treated mice, based on the weight of the animal body and their general behavior[1]. Animal Model: Four-week-old male mice (strain: C.B-17/IcrHsd-Prkdcscid for C4-2B) with C4-2B mouse xenograft model[1] Dosage: 50 mg/kg, 100 μL Administration: Intraperitoneal (i.p.) injection, 5 times per week, 25 days Result: Exhibited strong antitumor activities during the 25-day treatment period, with a tumor growth inhibition (TGI) of 51%.

[1]. Zhang M, et al. Structure-Based Discovery and Optimization of Benzo[ d]isoxazole Derivatives as Potent and Selective BET Inhibitors for Potential Treatment of Castration-Resistant Prostate Cancer (CRPC). J Med Chem. 2018 Apr 12;61(7):3037-3058.