CCT241533-hydrochloride _Checkpoint Kinase (Chk) 抑制剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECCT241533 hydrochlorideCat. No.: HY-14715BCAS No.: 1431697-96-9分式: CHClFNO分量: 478.94作靶点: Checkpoint Kinase (Chk)作通路: Cell Cycle/DNA Damage储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 100

2、 mg/mL (208.79 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.0879 mL 10.4397 mL 20.8794 mL5 mM 0.4176 mL 2.0879 mL 4.1759 mL10 mM 0.2088 mL 1.0440 mL 2.0879 mL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，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶

3、剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.22 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.22 mM); Clear solution3. 请依序添加每种溶剂： 10% DMS

4、O 90% corn oil1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (5.22 mM); Clear solutionBIOLOGICAL ACTIVITY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。IC50 & Target Chk2 Chk13 nM (IC50) 245 nM (IC50)体外研究 CCT241533 hydrochloride inhibits CHK2 with an

5、IC50 of 3 nM and shows minimal cross reactivity against apanel of kinases at 1 M. 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 byinhibition of CHK2 autophosphorylation

6、 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 C

7、HK2 signal is seen with a PARP inhibitor alone and this activation is abolishedby CCT241533. The cytotoxicity of CCT241533 in HT-29, HeLa and MCF-7, measured as the growthinhibitory IC50(GI50) by SRB assay, is 1.7, 2.2 and 5.1 M, respectively 1. CCT241533 hydrochloride is apotent CHK2 inhibitor (IC5

8、0=3 nM), with selectivity (63-fold) over CHK1(IC50=190 nM) and low hERGinhibition (IC50=22 M) 2.PROTOCOLCell Assay 1 HT-29, HeLa and MCF-7 cells are exposed to a fixed concentration (GI50) of CCT241533 in combinationwith increasing concentrations of either PARP inhibitor or cytotoxic drug in a 96 ho

9、ur SRB assay or 7-10 daycolony forming assay. The ability of CCT241533 to enhance cell killing is expressed as a potentiation index(PI) which is the ratio of GI50 for the genotoxic or PARP inhibitor alone: GI50 for the genotoxic or PARPinhibitor in combination with a CHK2 inhibitor. Thus PI1 indicat

10、es potentiation and PI 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 J Chem Inf Model. 2017 Nov 27;57(11):2699-2706.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Anderson VE, et al. CCT241533 is a potent and selec

11、tive inhibitor of CHK2 that potentiates the cytotoxicity of PARP inhibitors. CancerRes. 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 MedChem. 2011 Jan 27;54(2):580-90.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEMcePdfHeightCaution: Product has no