CCT241533 hydrochloride

"目录号: HY-14715B

Cell Cycle/DNA Damage-

CCT241533 hydrochloride 是一种有效的选择性 ATP 竞争性的CHK2抑制剂，IC50为 3 nM，Ki为 1.16 nM。

Checkpoint Kinase (Chk)

相关产品

LY2606368-AZD-7762-SCH900776-LY2603618-CCT245737-CHIR-124-BML-277-PF 477736-CCT244747-CCT241533-

生物活性

Description

CCT241533 hydrochloride is a potent and selective ATP competitive inhibitor ofCHK2with anIC50of 3 nM andKiof 1.16 nM.

IC50& Target

IC50: 3 nM (CHK2)[1]

Ki: 1.16 nM (CHK2)[1]

In Vitro

CCT241533 hydrochloride inhibits CHK2 with an IC50of 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 IC50(GI50) by SRB assay, is 1.7, 2.2 and 5.1 μM, respectively[1]. CCT241533 hydrochloride is a potent CHK2 inhibitor (IC50=3 nM), with selectivity (63-fold) over CHK1(IC50=190 nM) and low hERG inhibition (IC50=22 μM)[2].

References

[1].Anderson VE, et al. CCT241533 is a potent and selective inhibitor of CHK2 that potentiates the cytotoxicity of PARP inhibitors. Cancer Res. 2011 Jan 15;71(2):463-72.

[2].Caldwell JJ, et al. Structure-based design of potent and selective 2-(quinazolin-2-yl)phenol inhibitors of checkpoint kinase 2. J Med Chem. 2011 Jan 27;54(2):580-90.