CCT241533盐酸盐 | 1431697-96-9

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: CCT241533盐酸盐
• 英文名称: CCT241533 hydrochloride
• 英文别名: 4-fluoro-2-[4-[[(3S,4R)-4-(2-hydroxypropan-2-yl)pyrrolidin-3-yl]amino]-6,7-dimethoxyquinazolin-2-yl]phenol;hydrochloride
• CAS: 1431697-96-9
• 化学式: C23H28ClFN4O4
• 分子量: 478.9
• InChiKey: LAKJUTZIXHTMPC-SSPJITILSA-N

物化性质

• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  3.35
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  109
• 氢给体数：
  5
• 氢受体数：
  9

制备方法与用途

生物活性

CCT241533 hydrochloride是有效，选择性的 CHK2 抑制剂，IC50 和 Ki 分别为 3 nM 和 1.16 nM。

靶点

Chk2 3 nM (IC 50 )

Chk1 245 nM (IC 50 )

Chk2 1.16 nM (Ki)

体外研究

CCT241533 hydrochloride inhibits CHK2 with an IC ₅₀ of 3 nM and shows minimal cross reactivity against a panel of kinases at 1 μM. X-ray crystallography confirms that CCT241533 binds to CHK2 in the ATP pocket. CCT241533 blocks CHK2 activity in human tumor cell lines in response to DNA damage, as demonstrated by inhibition of CHK2 autophosphorylation at S516, band-shift mobility changes and HDMX degradation. CCT241533 does not potentiate the cytotoxicity of a selection of genotoxic agents in several cell lines. However, CCT241533 significantly potentiates the cytotoxicity of two structurally distinct PARP inhibitors. Clear induction of the pS516 CHK2 signal is seen with a PARP inhibitor alone and this activation is abolished by CCT241533. The cytotoxicity of CCT241533 in HT-29, HeLa and MCF-7, measured as the growth inhibitory IC ₅₀ (GI ₅₀ ) by SRB assay, is 1.7, 2.2 and 5.1 μM, respectively. CCT241533 hydrochloride is a potent CHK2 inhibitor (IC ₅₀ =3 nM), with selectivity (63-fold) over CHK1(IC ₅₀ =190 nM) and low hERG inhibition (IC ₅₀ =22 μM).