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].

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.