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dBET1

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Chemical Structure| 1799711-21-9 同义名 : -
CAS号 : 1799711-21-9
货号 : A290656
分子式 : C38H37ClN8O7S
纯度 : 99%+
分子量 : 785.268
MDL号 : MFCD31544503
存储条件：

粉末 Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 45 mg/mL(57.31 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, IC50:20 nM
描述 dBET1 is a PROTAC, consisting of a BRD4-ligand JQ-1 linkerd to a cereblon E3 ligase ligand, targeting on BET bromodomain BRD4 with DC50 values of < 100nM and 140nM for degradation of BRD4 protein in MV4-11 cells post 18-hour treatment and in H661 cells post 4-hour treatment. dBET1 exhibited a bell-shaped dose−response curve in the cereblon/PROTAC/BRD4 proximity assay[1]. Treatment with dBET1 resulted a depletion of BRD4 in MV4;11 cells at concentration ranging in 0.1-10μM post 18h and a downregulation of BRD4 by 95 at concentration of 100nM post 2h. Similarly, a dose-dependent degradation of BRD4 could be observed in MM1S cells exposure to dBET1 at concentration ranging in 0.5-10μM post 18-hour treatment. The degradation of BRD4 by treatment with 250nM dBET1 for 2h led a decrease of transcription of BRD2, BRD3, MYC and PIM1 targeted by BRD4, in MV4;11 cells. dBET1 at concentration of 0.25μM, 1μM and 2.5μM caused apoptosis of MV4;11 and DHL4 cells more potently than JQ1 post 24h, which could be marked by cleaved PARP and Caspase-3 at 4h or 8h. Similar increase of apoptosis of primary AML cells could be observed by treatment with 1μM and 10μM dBET1 post 24h. Intraperitoneal administration of 50mg/kg dBET1 daily for 14 days achieved suppression of tumor growth MV4;11 xenograft mice. Decreased leukemic burden in bone marrow could be achieved by 19-day administration. dBET1(R) works as a negative control of dBET1[2].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.27mL

0.25mL

0.13mL

6.37mL

1.27mL

0.64mL

12.73mL

2.55mL

1.27mL
参考文献

[1]Wurz RP, Dellamaggiore K, et al. A "Click Chemistry Platform" for the Rapid Synthesis of Bispecific Molecules for Inducing Protein Degradation. J Med Chem. 2018 Jan 25;61(2):453-461.

[2]Winter GE, Buckley DL, et al. DRUG DEVELOPMENT. Phthalimide conjugation as a strategy for in vivo target protein degradation. Science. 2015 Jun 19;348(6241):1376-81.