BETd-260

BETd-260 (ZBC 260) is a BET PROTAC degrader. BETd-260 recruits BRD2, BRD3, and BRD4 to the CUL4-RBX1-DDB1-CRBN E3 ubiquitin ligase complex, driving cereblon-, proteasome-, and NEDD8-activating enzyme-dependent ubiquitination and degradation, with a DC50 of approximately 30-100 pM in RS4;11 cells. BETd-260 induces cancer cell apoptosis via endogenous signaling pathways, regulates the expression of the Bcl-2 family, inhibits the oncogene c-Myc, and reduces cell viability. BETd-260 suppresses tumor growth in mouse xenograft models with good biosafety. BETd-260 can be used in research related to acute leukemia, hepatocellular carcinoma, osteosarcoma, and triple-negative breast cancer^[1][2][3][4]. IC50 & Target:BRD4^[1]
PROTAC In Vitro:BETd-260 (for 4 days) potently inhibits the proliferation of RS4;11 human acute leukemia cells, with an IC₅₀ of 51 pM^[1].
BETd-260 (for 4 days) inhibits the proliferation of human acute leukemia cell line MOLM-13, with an IC₅₀ of 2.2 nM^[1].
BETd-260 (0.1-1 nM; 3 h) potently degrades BRD2, BRD3 and BRD4 proteins in the human acute leukemia cell line RS4;11^[1].
BETd-260 (0.03-10 nM; 24 h) degrades BRD2, BRD3 and BRD4 proteins in RS4;11 human acute leukemia cells and downregulates c-Myc^[1].
BETd-260 (1 nM; 3 h, preceded by 2 h pretreatment) induces the degradation of BRD2, BRD3 and BRD4 in human acute leukemia cell line RS4;11, and this process depends on binding to BET proteins, cereblon, the proteasome and NEDD8-activating enzyme^[1].
BETd-260 (10-100 nM; 1-48 h) rapidly and potently degrades BRD2, BRD3 and BRD4 proteins in human hepatocellular carcinoma HepG2 cells^[2].
BETd-260 (100 nM; 24 h) exhibits broad BET protein degradation activity in human hepatocellular carcinoma (HCC) cell lines, completely eliminating BRD2, BRD3 and BRD4 in BEL-7402, SK-HEP-1 and SMMC-7721 cells, and reducing the levels of these proteins to low levels in HuH-7 and MHCC97H cells^[2].
BETd-260 (72 h) potently inhibits the cell viability of MNNG/HOS, Saos-2, MG-63 and SJSA-1 osteosarcoma cell lines, with EC₅₀ values ranging from 1.1 nM to 16.1 nM^[3].
BETd-260 (3-30 nM; 1-24 h) potently degrades BRD2, BRD3 and BRD4 in MNNG/HOS, Saos-2, MG-63 and SJSA-1 osteosarcoma cell lines^[3].
BETd-260 (10 nM; 2 h, preceded by 1 h pre-treatment with inhibitors) induces the degradation of BRD2, BRD3 and BRD4 in MNNG/HOS osteosarcoma cells via a pathway mediated by the Cullin-dependent E3 ligase and ubiquitin-proteasome system, and this degradation process depends on specific binding to BET proteins^[3].
BETd-260 potently inhibits the growth of human triple-negative breast cancer (TNBC) cell lines^[4].
BETd-260 efficiently degrades BRD2, BRD3 and BRD4 proteins in human triple-negative breast cancer (TNBC) cell lines^[4].
BETd-260 (0.3-30 nM; 24 h) induces cell cycle arrest and significant apoptosis in RS4;11 and MOLM-13 human acute leukemia cells^[1].
BETd-260 (72 h) potently and dose-dependently inhibits the viability of human HepG2, BEL-7402, SK-HEP-1, SMMC-7721, HuH-7 and MHCC97H hepatocellular carcinoma cells, with EC₅₀ values ranging from 5.4 to 64.9 nM^[2].
BETd-260 (10-100 nM; 48 h) induces extensive apoptosis in human HepG2, BEL-7402, SK-HEP-1, SMMC-7721, HuH-7 and MHCC97H hepatocellular carcinoma cells^[2].
BETd-260 (10-100 nM; 24 h) activates the apoptotic signaling pathway in human HepG2, BEL-7402, SK-HEP-1, SMMC-7721, HuH-7 and MHCC97H hepatocellular carcinoma cells, and induces PARP cleavage and caspase-3 activation^[2].
BETd-260 (10-100 nM; 24 h) bidirectionally regulates the expression of apoptosis-related proteins, inhibits c-Myc expression, upregulates Bad expression, and downregulates the expressions of Mcl-1, Bcl-2, XIAP and c-Myc in human hepatocellular carcinoma cells^[2].
BETd-260 (100 nM; 48 h following 24 h siRNA transfection) induces cell death in human HepG2 and BEL-7402 hepatocellular carcinoma cells, and this process depends on the endogenous caspase-9-mediated apoptotic pathway rather than the exogenous caspase-8 pathway^[2].
BETd-260 (100 nM; 48 h after 24 h siRNA transfection) induces cell death in human HepG2 and BEL-7402 hepatocellular carcinoma cells in a Bad-dependent manner^[2].
BETd-260 (10-100 nM; 24 h) disrupts mitochondrial membrane integrity in human HepG2 and BEL-7402 hepatocellular carcinoma cells, and induces the release of cytochrome c from mitochondria into the cytosol^[2].
BETd-260 (10-100 nM; 4-24 h) upregulates the expression of Bad mRNA in human HepG2 and BEL-7402 hepatocellular carcinoma cells in a dose-dependent manner^[2].
BETd-260 (3-30 nM; 24 h) induces dose-dependent apoptosis in MNNG/HOS and Saos-2 osteosarcoma cells^[3].
BETd-260 (3-30 nM; 24 h) activates the mitochondrial apoptotic pathway in MNNG/HOS and Saos-2 osteosarcoma cells, which is evidenced by the cleavage of caspase-3, caspase-9 and PARP-1^[3].
BETd-260 (10 nM; 24-48 h, with 1 h pre-treatment with inhibitors) induces death and apoptosis in MNNG/HOS and Saos-2 osteosarcoma cells, a process that mainly relies on the endogenous pathway mediated by the caspase-9 and caspase-3 cascade^[3].
BETd-260 (3-30 nM; 1-24 h) regulates the expression of Bcl-2 family members in MNNG/HOS and Saos-2 osteosarcoma cells, and inhibits c-Myc (without affecting p53), specifically characterized by depletion of Mcl-1 and Bcl-xl, upregulation of Noxa levels, and reduction of c-Myc levels^[3]. In Vivo:BETd-260 (compound 23) (5 mg/kg; intravenous injection; once every two days; for 3 consecutive weeks) induces regression of RS4;11 xenograft tumors in SCID mice, and triggers sustained degradation of BET proteins, downregulation of c-Myc expression, and apoptosis in tumor tissues^[1].
BETd-260 (5 mg/kg; intravenous injection; single administration / three times per week; for 3 consecutive weeks) exerts potent anti-hepatocellular carcinoma activity in vivo. It inhibits tumor growth in HepG2 and BEL-7402 xenograft models by degrading BET proteins, regulating apoptosis regulators, and inducing tumor cell apoptosis^[2].
BETd-260 (5 mg/kg; intravenous injection; three times per week; for 3 consecutive weeks) inhibits tumor growth in the MNNG/HOS osteosarcoma xenograft model of BALB/c mice, with durable efficacy and no observed toxicity^[3].
BETd-260 (5 mg/kg; intravenous injection; three times per week; for 4 consecutive weeks) inhibits tumor growth in an osteosarcoma PDX xenograft model in NOD SCID mice, with no observed toxicity^[3].
BETd-260 (5 mg/kg; intravenous injection; 3 times per week; for 3 consecutive weeks) inhibits the growth of MDA-MB-231 and MDA-MB-468 xenograft tumors, with activity comparable to or stronger than that of BETi-211 (HY-122703). It also depletes BET proteins, upregulates p21^WAF1 and downregulates MCL1 in tumors, without significant toxicity^[4].