CPI-455
(Synonyms: 6-异丙基-7-氧代-5-苯基-4,7-二氢吡唑并[1,5-A]嘧啶-3-腈) 目录号 : GC10774
A KDM5 inhibitor
Cas No.:1628208-23-0
Sample solution is provided at 25 µL, 10mM.
IC50: 10 nM
CPI-455 is a KDM5 inhibitor.
The KDM5 family of histone demethylases catalyzes the demethylation of histone H3 on lysine 4 (H3K4) and is required for the survival of drug-tolerant persister cancer cells (DTPs).
In vitro: Previous study found that CPI-455 could potently inhibit the fulllength KDM5A in enzymatic assays with a half-maximal inhibitory concentration of 10 ± 1 nM. CPI-455 inhibited KDM5A, KDM5B and KDM5C to similar levels but showed significantly weaker potency toward KDM4C and KDM7B (~200- and 770-fold, respectively) and no detectable inhibition of KDM2B, KDM3B or KDM6A. Moreover, it was found that the CPI-455-mediated KDM5 inhibition led to a dose-dependent increase in global H3K4me3 in HeLa cells, and the removal of CPI-455 resulted in a rapid reversal of H3K4me3 increases in HeLa cells. Moreover, CPI-455 could delay the appearance of heavy H3K4me3, which was consistent with the role for KDM5 enzymes in H3K4me3 turnover, however, the turnover of H3K4me2 was only marginally altered. As expected, CPI-455 could affect the turnover of H3K4 monomethylation [1].
In vivo: So far, there is no animal in vivo data reported.
Clinical trial: Up to now, CPI-455 is still in the preclinical development stage.
Reference:
[1] Vinogradova M, et al. An inhibitor of KDM5 demethylases reduces survival of drug-tolerant cancer cells. Nat Chem Biol. 2016 Jul;12(7):531-8.
Cell experiment: | MCF-7 is a luminal breast cancer cell line. MCF-7 is grown in MEM supplemented with 10% fetal bovine serum (FBS) and is incubated at 37°C with a 5% CO2 atmosphere. For each treatment condition, 2.5×105 MCF-7 cells are plated in T25 flask and allowed to rest overnight. The following day, the media is aspirated and replaced with media containing DAC at a final concentration of 62.5 nM. DAC media is aspirated and replaced every 24 hours for a total treatment time of 72 hours. Following DAC treatment, media is aspirated and replaced with media supplemented with 2% FBS containing KDM5 inhibitors (e.g., CPI-455) at a final concentration of 9.375 μM. Cells are harvested following 72 hours of KDM5 inhibitor treatment[1]. |
References: [1]. Vinogradova M, et al. An inhibitor of KDM5 demethylases reduces survival of drug-tolerant cancer cells. Nat Chem Biol. 2016 Jul;12(7):531-8. | |
| Cas No. | 1628208-23-0 | SDF | |
| 别名 | 6-异丙基-7-氧代-5-苯基-4,7-二氢吡唑并[1,5-A]嘧啶-3-腈 | ||
| 化学名 | 6-isopropyl-7-oxo-5-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitrile hydrochloride | ||
| Canonical SMILES | N#CC1=C(NC(C2=CC=CC=C2)=C(C(C)C)C3=O)N3N=C1.Cl | ||
| 分子式 | C16H15ClN4O | 分子量 | 314.77 |
| 溶解度 | ≥ 31.5mg/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 | 3.1769 mL | 15.8846 mL | 31.7692 mL |
| 5 mM | 0.6354 mL | 3.1769 mL | 6.3538 mL |
| 10 mM | 0.3177 mL | 1.5885 mL | 3.1769 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。
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet