BETd-246 (C09-1113-082)

BETd-246 is a second-generation and PROTAC -based BET bromodomain (BRD) inhibitor connected by ligands for Cereblon and BET , exhibiting superior selectivity, potency and antitumor activityIn VitroBETd-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 induces a rapid and time-dependent downregulation of MCL1 protein in all the TNBC cell lines evaluated. BETd-246 induces much stronger apoptosis than BETi-211. BETd-246 (100 nM, 24 hours) induces pronounced cell cycle arrest and apoptosis in TNBC cell lines. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Proliferation AssayCell Line: MDA-MB-468 cells Concentration: 100 nM Incubation Time: 24 or 48 hours Result: Displayed strong growth inhibition and apoptosis induction activity in TNBC cell lines. Cell Cycle AnalysisCell Line: Human TNBC cells Concentration: 100 nM Incubation Time: 24 hours Result: Induced pronounced cell cycle arrest and apoptosis in TNBC cell lines. Western Blot AnalysisCell Line: Human TNBC cells Concentration: 0-100 nM Incubation Time: 1-3 hours Result: Caused a dose-dependent depletion of BRD2, BRD3 and BRD4.In VivoBETd-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. The treatment of 10 mg/kg induces partial tumor regression during treatment without apparent toxicity. BETd-246 has very limited drug exposure in the xenograft tumor tissue in MDA-M-231and MDA-MB-468 models . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: “Washington Human in Mouse (WHIM)” (PDX) model developed from a patient with treatment-resistant breast cancer (ESR E380Q , PR- and HER2-)) . Dosage: 5, 10 mg/kg Administration: IV, 3 times per week for 3 weeks. Result: Effectively inhibited WHIM24 tumor growth.Form:SolidIC50& Target:BET BRD. Specification: 0.98 Molecular Formula: C48H55N11O10 Molecular Weight: 946.02 PubChem CID: 131698640