6-Isopropyl-7-oxo-5-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitrile hydrochloride

Names

[ CAS No. ]:
2095432-28-1

[ Name ]:
6-Isopropyl-7-oxo-5-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitrile hydrochloride

[Synonym ]:
6-Isopropyl-7-oxo-5-phenyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitrile hydrochloride (1:1)
Pyrazolo[1,5-a]pyrimidine-3-carbonitrile, 4,7-dihydro-6-(1-methylethyl)-7-oxo-5-phenyl-, hydrochloride (1:1)

Biological Activity

[Description]:

CPI-455 hydrochloride is a specific, pan-KDM5 inhibitor with an IC50 of 10 nM for KDM5A. CPI-455 hydrochloride mediates KDM5 inhibition, elevates global levels of H3K4me3, and decreases the number of drug-tolerant persister cancer cells in multiple cancer cell line models treated with standard chemotherapy or targeted agents[1].

[Related Catalog]:

Research Areas >> Cancer
Signaling Pathways >> Epigenetics >> Histone Demethylase

[Target]

KDM5


[In Vitro]

CPI-455 hydrochloride 介导 KDM5 抑制，提高 H3K4 三甲基化 (H3K4me3) 的总体水平，并减少使用标准化疗或靶向药物治疗的多种癌细胞系模型中的 DTP 数量[1]。 CPI-455 盐酸盐，对目标 KDM5 蛋白具有高亲和力。在 24 小时内，在暴露于两种活性化合物 CPI-455 和 CPI-766 中的任何一种后，观察到 H3K4me3 以剂量依赖性方式增加。 KDM5 Inhibitor CPI0455 在 3 种管腔乳腺癌细胞系 MCF-7、T-47 和 EFM-19 中的 IC50 计算值分别为 35.4、26.19 和 16.13 μM[2]。

[In Vivo]

在小鼠体内双重阻断 B7-H4 和 KDM5B（CPI-455 hydrochloride，50/70 mg/kg，腹腔注射，每日）可引发保护性免疫[2]。

[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.  

[2]. Benjamin R. Leadem. NOVEL HISTONE DEMETHYLASE INHIBITORS SYNERGISTICALLY

[3]. Xiang Yuan, et al. Blockade of Immune-Checkpoint B7-H4 and Lysine Demethylase 5B in Esophageal Squamous Cell Carcinoma Confers Protective Immunity against P. gingivalis Infection. Cancer Immunol Res. 2019 Sep;7(9):1440-1456.  

Chemical & Physical Properties

[ Molecular Formula ]:
C16H15ClN4O

[ Molecular Weight ]:
314.770

[ Exact Mass ]:
314.093445

[ Storage condition ]:
Inert atmosphere,2-8°C