BETd-246 is an inhibitor of second-generation and PROTAC-based BET bromodomain (BRD), show antitumor activity.

BETd-246 treatment (0-100 nM, 1-3 h) causes a dose-dependent depletion of BRD2, BRD3 and BRD4 in representative TNBC cell lines with 30-100 nM for 1 h or with 10-30 nM for 3 h incubation. BETd-246 (100 nM, 24/48 hours) displays strong growth inhibition and apoptosis induction activity in MDA-MB-468 cell lines. BETd-246 (100 nM, 24 hours) induces pronounced cell cycle arrest and apoptosis in TNBC cell lines[1]. BETd-246 induces a rapid and time-dependent downregulation of MCL1 protein in all the TNBC cell lines evaluated and it also induces much stronger apoptosis than BETi-211.

BETd-246 (5 mg/kg, IV, 3 times per week for 3 weeks) treatment effectively inhibits WHIM24 tumor growth, similar to the antitumor activity of BETi-211 with higher dosage and more frequently administration. BETd-246 has very limited drug exposure in the xenograft tumor tissue in MDA-M-231and MDA-MB-468 models[1]. The treatment of 10 mg/kg induces partial tumor regression during treatment without apparent toxicity.

2140289-17-2

C48H55N11O10

946.02

DMSO:200 mg/mL (211.41 mM),Need ultrasonic
Powder: -20°C for 3 years
In solvent: -80°C for 2 years