产品说明书

dBET6

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Chemical Structure| 1950634-92-0 同义名 : -
CAS号 : 1950634-92-0
货号 : A475199
分子式 : C42H45ClN8O7S
纯度 : 99%+
分子量 : 841.374
MDL号 : MFCD31692407
存储条件：

粉末 Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(59.43 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • BET

    BRD4, IC50:14 nM
描述 dBET6 is an optimized and highly cell-permeable chemical degrader of BET bromodomain proteins, based on PROTAC. Incubation with dBET6 at concentration ranging in 0.1nM-1μM for 3h led to dose-dependent degradation of BRD2, BRD3, BRD4 via proteasome in cells. Treatment with 100 nM dBET6 for 1h caused degradation of BRD4 relying on E3 ubiquitin ligase CRBN and subsequent downregulation of c-MYC and induction of apoptosis in T-ALL (T cell acute lymphoblastic leukemia) cells. Intraperitoneal injection with dBET6 at dose of 7.5mg/kg, BID, for 18 days significantly inhibited tumor growth in SUPT11 xenograft mice with degradation of BRD4 in vivo, as well as exhibited a significant survival benefit in MOLT4 xenograft mice compared to vehicle control or JQ1-treated group. Degradation of BET by dBET6 causes a collapse of global elongation that phenocopies CDK9 inhibition, attenuating p-TEFb activity independent of recruitment with a specific downregulation of Ser2 phosphorylation observed[1].
作用机制 dBET6 is chemical degrader of BET bromodomain proteins based on PROTAC and led a collapse of global elongation that phenocopies CDK9 inhibition.[1]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.19mL

0.24mL

0.12mL

5.94mL

1.19mL

0.59mL

11.89mL

2.38mL

1.19mL
参考文献

[1]Winter GE, Mayer A, et al. BET Bromodomain Proteins Function as Master Transcription Elongation Factors Independent of CDK9 Recruitment. Mol Cell. 2017 Jul 6;67(1):5-18.e19.