CCT241736

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

CCT241736 是一种口服生物可利用的双重 FLT3/Aurora 激酶抑制剂，还可抑制临床相关的 FLT3 耐药突变体，包括 FLT3-ITD 和 FLT3。

CCT241736 is a potent and orally active and dual FLT3-Aurora inhibitor. CCT241736 has IC50 values against FLT3, Aurora A and Aurora B of 0.035, 0.015 and 0.1 μM respectively. CCT241736 inhibits a wide range of FLT3 mutants, including FLT3-ITD, -D835Y, -D835H, -K663Q and -N841I. In cellular assays, CCT241736 inhibits viability of the human FLT3-ITD positive AML cell lines MOLM-13 and MV-4;11 with EC50 values of 0.1 and 0.27.

CCT241736 (Compound 27e) is a potent and orally bioavailable dual FLT3 and Aurora kinase inhibitor, which inhibits Aurora kinases (Aurora-A Kd, 7.5 nM, IC50, 38 nM, Aurora-B Kd, 48 nM), FLT3 kinase (Kd, 6.2 nM), and FLT3 mutants including FLT3-ITD (Kd, 38 nM) and FLT3(D835Y) (Kd, 14 nM). CCT241736 exhibits antiproliferative activity in a range of human tumor cell lines, such as HCT116 human colon carcinoma (GI50, 0.300 μM), the human FLT3-ITD positive AML cell lines MOLM-13 (GI50, 0.104 μM) and MV4-11 (GI50, 0.291 μM). CCT241736 also inhibits both the autophosphorylation of Aurora-A at T288 (a biomarker for Aurora-A inhibition: IC50, 0.030 μM) and histone H3 phosphorylation at S10 (a biomarker for Aurora-B inhibition: IC50, 0.148 μM), consistent with potent cellular activity versus both Aurora-A and -B. CCT241736 suppresses Aurora-A in MOLM-13 cells with concomitant inhibition of FLT3 signaling.

CCT241736 (50, 100 mg/kg, b.i.d, p.o.) dose-dependently suppresses the growth of MV4-11 human tumor xenografts, and completely abolishes the tumors at 100 mg/kg via p.o. administration twice a day.

CCT241736 | CCT-241736 | CCT 241736

GPCR/G Protein

Dopamine Receptor

FLT3|Aurora Kinase

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1402709-93-6

456.37

C22H23Cl2N7

>98% (HPLC)

DMSO : 75 mg/mL 164.34 mM; H2O : < 0.1 mg/mL

Cc5nn(C)cc5c3nc4ncc(Cl)c(N2CCN(Cc1ccc(Cl)cc1)CC2)c4n3

6-chloro-7-[4-[(4-chlorophenyl)methyl]-1-piperazinyl]-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine

(-20℃)

With Ice Pack

≥ 2 years