BETd-260 (C09-1113-105)

BETd-260 (ZBC 260) is a PROTAC connected by ligands for Cereblon and BET , with as low as 30 pM against BRD4 protein in RS4;11 leukemia cell line BETd-260 potently suppresses cell viability and robustly induces apoptosis in hepatocellular carcinoma (HCC) cells .In VitroBETd-260 (ZBC260; Compound 23) is capable of inducing degradation of BRD2, BRD3, and BRD4 proteins at 30–100 pM in the RS4;11 leukemia cells. BETd-260 shows inhibitory activity against the growth of RS4;11 leukemia cells and MOLM-13 cells with IC 50 s of 51 pM and 2.2 nM, respectively, and induces apoptosis in both RS4;11 and MOLM-13 cell lines at 3-10 nM. BETd-260 reciprocally modulates the expression of several apoptotic genes in HCC cells, i.e., suppressing the expression of anti-apoptotic Mcl-1, Bcl-2, c-Myc, and XIAP, whereas increasing the expression of pro-apoptotic Bad. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoBETd-260 (5 mg/kg, i.v., every other day, thrice a week for 3 weeks) causes rapid tumor regression with a maximum of >90% regression in mice bearing RS4;11 xenograft tumors, and with no body weight loss or other signs of toxicity in mice. BETd-260 (5 mg/kg, i.v.) degrades the BRD2, BRD3, and BRD4 proteins for more than 24 h, with robust cleavage of PARP and caspase-3, and strong down-regulation of c-Myc protein in RS4;11 xenograft mice model . MCE has not independently confirmed the accuracy of these methods. They are for reference only.Form:SolidIC50& Target:BRD4 <30 pM (IC 50 ) BRD2 30-100 pM (IC 50 ) BRD3 30-100 pM (IC 50 ). Specification: 0.99 Molecular Formula: C43H46N10O6 Molecular Weight: 798.89 PubChem CID: 131698639 Isomeric SMILES: CCN1C(=CC(=N1)C2CC2)NC3=NC(=NC4=C3C5=CC(=C(C=C5N4)C6=C(ON=C6C)C)OC)C(=O)NCCCCCC7=C8CN(C(=O)C8=CC=C7)C9CCC(=O)NC9=O