CPI-203

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 100-500nM¹. 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 LSCs². 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 mice³.

溶解方案(细胞实验)

DMSO 中的溶解度 : ≥ 47 mg/mL (117.53 mM; 吸湿的 DMSO 对产品的溶解度有显著影响，请使用新开封的 DMSO)|* "≥" means soluble, but saturation unknown.

溶解方案(动物实验)

"方案 一": "请依序添加每种溶剂：10% DMSO 40% PEG300 5% Tween-80 45% SalineSolubility: ≥ 2.5 mg/mL (6.25 mM); 澄清溶液 此方案可获得 ≥ 2.5 mg/mL（饱和度未知）的澄清溶液。以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；再向上述体系中加入 50 μL Tween-80，混合均匀；然后再继续加入 450 μL 生理盐水 定容至 1 mL。生理盐水的配制：将 0.9 g 氯化钠，溶解于 ddH₂O 并定容至 100 mL，可以得到澄清透明的生理盐水溶液。"

"方案 二": "请依序添加每种溶剂：10% DMSO 90% (20% SBE-β-CD in Saline)Solubility: ≥ 2.5 mg/mL (6.25 mM); 澄清溶液 此方案可获得 ≥ 2.5 mg/mL（饱和度未知）的澄清溶液。以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液 中，混合均匀。2 g SBE-β-CD（磺丁基醚 β-环糊精）粉末定容于 10 mL 的生理盐水中，完全溶解至澄清透明。"

"方案 三": "请依序添加每种溶剂：10% DMSO 90% Corn OilSolubility: ≥ 2.5 mg/mL (6.25 mM); 澄清溶液 此方案可获得 ≥ 2.5 mg/mL（饱和度未知）的澄清溶液，此方案实验周期在半个月以上的动物实验酌情使用。以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。"