CPI-203
目录号 : GC14699
A bioavailable inhibitor of BET bromodomains
Cas No.:1446144-04-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
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Cell lines |
9 MCL cell lines and 2 PBMCs |
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Preparation method |
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
72 hrs |
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Applications |
In 9 MCL cell lines, CPI-203 exerted a cytostatic effect, with a mean GI50 value of 0.23 μM. At this concentration, the cytotoxicity of CPI-203 to PBMCs was below 25%, which demonstrated its selectivity. In 2 Bortezomib-resistant MCL cell lines with high MYC expression (REC-1 and JBR) and 2 Bortezomib-sensitive MCL cell lines with lower MYC expression (GRANTA-519 and JVM-2), CPI-203 at the dose of 5 μM effectively reduced MYC expression, without causing apoptosis. |
| Animal experiment [1]: | |
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Animal models |
REC-1 tumor-bearing mice |
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Dosage form |
2.5 mg/kg; i.p.; b.i.d. |
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Applications |
In REC-1 tumor-bearing mice, CPI-203 alone or in combination with Lenalidomide reduced tumor volume by 44% and 62%, respectively. Moreover, tumor glucose uptake was reduced by 86% in the CPI-203 + Lenalidomide group. Immunohistochemical analysis of tumors collected from the CPI-203 + Lenalidomide group showed a decrease in the mitotic index, almost complete disappearance of MYC- and IRF4-positive cells, as well accumulation of cleaved caspase-3-positive cells. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Moros A, Rodríguez V, Saborit-Villarroya I, Montraveta A, Balsas P, Sandy P, Martínez A, Wiestner A, Normant E, Campo E, Pérez-Galán P, Colomer D, Roué G. Synergistic antitumor activity of lenalidomide with the BET bromodomain inhibitor CPI203 in bortezomib-resistant mantle cell lymphoma. Leukemia. 2014 Mar 18. | |
CPI-203 is a potent, selectivie and competitive small molecule inhibitor of BET bromodomain with a mean GI50 value of 0.23μM in MCL cell lines [1].
As an inhibitor of BET proteins, CPI-203 inhibits BRD4 in vitro and in cells. It inhibits the specific Ser2 phosphorylation of both endogenous BRD4 and exogenous mutant BRD4 (BRD4 FEE-AAA) in vivo, thus blocking the recruitment of BRD4 to chromatin. CPI-203 is shown to suppress cell growth of 9 MCL cell lines. And in REC-1 cells, treatment of CPI-203 causes the effects of IRF4 expression. CPI-203 marginally activates the apoptotic program in these cells. The CPI-203-lenalidomide combination is reported to be a promising strategy in MCL cases refractory to proteasome inhibition [1, 2].
References:
[1] Moros A, Rodríguez V, Saborit-Villarroya I, Montraveta A, Balsas P, Sandy P, Martínez A, Wiestner A, Normant E, Campo E, Pérez-Galán P, Colomer D, Roué G. Synergistic antitumor activity of lenalidomide with the BET bromodomain inhibitor CPI203 in bortezomib-resistant mantle cell lymphoma. Leukemia. 2014 Mar 18.
[2] Devaiah BN, Lewis BA, Cherman N, Hewitt MC, Albrecht BK, Robey PG, Ozato K, Sims RJ 3rd, Singer DS. 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.
| Cas No. | 1446144-04-2 | SDF | |
| 化学名 | (S)-2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetamide | ||
| Canonical SMILES | CC1=C(C)C(C(C2=CC=C(Cl)C=C2)=N[C@@H](CC(N)=O)C3=NN=C(C)N43)=C4S1 | ||
| 分子式 | C19H18ClN5OS | 分子量 | 399.9 |
| 溶解度 | ≥ 40mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5006 mL | 12.5031 mL | 25.0063 mL |
| 5 mM | 0.5001 mL | 2.5006 mL | 5.0013 mL |
| 10 mM | 0.2501 mL | 1.2503 mL | 2.5006 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。