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CPI-203

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Chemical Structure| 1446144-04-2 同义名 : -
CAS号 : 1446144-04-2
货号 : A639214
分子式 : C19H18ClN5OS
纯度 : 98+%
分子量 : 399.897
MDL号 : MFCD27997886
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 45 mg/mL(112.53 mM)，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：

IP 2% DMSO+water 1 mg/mL clear

PO 0.5% CMC-Na 30 mg/mL suspension

生物活性
靶点

  • BET

    BRD4, IC50:37 nM
描述 The Bromodomain and Extra-Terminal Domain BET (Bromodomain and Extra-Terminal Domain) family is characterized by the presence of two tandem bromodomains and an extra-terminal domain. BET proteins can govern the assembly of histone acetylation-dependent chromatin complexes, thus regulating gene expression. CPI-203, the JQ1 derivative, is the inhibitor of BET bromodomain with IC50 value of 37nM (measured by BRD4 α-screen assay). CPI203 can inhibit BRD4 in vitro and in cells. MYC mRNA can be suppressed after 4h exposure to CPI203 with IC50 value of 99nM in MV4-11 acute myelogenous leukemia (AML) cell line. Pre-incubation with CPI-203 for 2h can suppress IL-6 release stimulated by LPS for 16h in THP-1, with IC50 value of 30nM. CPI-203 did not affect BRD4 kinase activity in vitro kinase assays. In contrast, in cells, specific Ser2 phosphorylation by either endogenous BRD4 or exogenous BRD4 FEE-AAA can be markedly decreased by treatment with CPI-203 on concentration of 100-500nM[1]. By inducing apoptosis and differentiation, RITA and CPI-203 synergize to drive CML CD34+ cell kill with combination indices (CIs) ranging from 0.07 to 0.34. Over 72h, combination of RITA with CPI-203 was also effective in synergistically eliminating residual CD34+CD38− cells (CI=0.3–0.8) in LSCs, suggesting the effect of RITA and CPI-203 on elimination of LSCs[2]. CPI203 also showed synergistic antitumor activity of lenalidomide in bortezomib-resistant mantle cell lymphoma. Treatment with combination of CP203 (2.5mg/kg, BID) with lenalidomide (50mg/kg, daily) for 16 days reduction in tumor volume reached 62% in REC-1 xenografted SCID mice[3].
作用机制 CPI-203 can suppress BRD4-mediated Pol II CTD Ser2 phosphorylation by specific inhibition of BRD4 recruitment to chromatin. [1]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.50mL

0.50mL

0.25mL

12.50mL

2.50mL

1.25mL

25.01mL

5.00mL

2.50mL
参考文献

[1]Devaiah BN, Lewis BA, et al. BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain. Proc Natl Acad Sci U S A. 2012 May 1;109(18):6927-32.

[2]Abraham SA, Hopcroft LE, et al. Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells. Nature. 2016 Jun 16;534(7607):341-6.

[3]Moros A, Rodr¨ªguez V, et al. Synergistic antitumor activity of lenalidomide with the BET bromodomain inhibitor CPI203 in bortezomib-resistant mantle cell lymphoma. Leukemia. 2014 Oct;28(10):2049-59