BETd-246

Research use only, not for human use.

A potent, second-generation BET protein degrader that exhibits superior selectivity, potency and antitumor activity.

A potent, second-generation BET protein degrader that exhibits superior selectivity, potency and antitumor activity; completely and selectively depletes 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; displays strong growth inhibition and apoptosis induction activity in TNBC cell lines with IC50 <1 uM, induces a rapid and time-dependent downregulation of MCL1 protein; decreases BET proteins in xenograft breast tumors and suppress tumor growth in vivo without causing weight loss.

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 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. Cell Proliferation Assay Cell 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 Analysis Cell 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 Analysis Cell Line:Human TNBC cells Concentration:0-100 nM Incubation Time:1-3 hours Result:Caused a dose-dependent depletion of BRD2, BRD3 and BRD4.

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. 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. Animal Model:“Washington Human in Mouse (WHIM)” (PDX) model developed from a patient with treatment-resistant breast cancer (ESRE380Q, PR- and HER2-)).Dosage:5, 10 mg/kg Administration:IV, 3 times per week for 3 weeks.Result:Effectively inhibited WHIM24 tumor growth.

BETd 246 | BETd246

PROTACs

PROTAC

PROTAC

——

——

2140289-17-2

946.035

C48H55N11O10

>98% (HPLC)

DMSO : 200 mg/mL 211.41 mM

CCN1C(=CC(=N1)C2CC2)NC3=NC(=NC4=C3C5=CC(=C(C=C5N4)C6=C(ON=C6C)C)OC)C(=O)NCCCOCCOCCOCCCNC7=CC=CC8=C7C(=O)N(C8=O)C9CCC(=O)NC9=O

4-((3-cyclopropyl-1-ethyl-1H-pyrazol-5-yl)amino)-7-(3,5-dimethylisoxazol-4-yl)-N-(3-(2-(2-(3-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)propoxy)ethoxy)ethoxy)propyl)-6-methoxy-9H-pyrimido[4,5-b]indole-2-carboxamide

(-20℃)

With Ice Pack

≥ 2 years