CCT241736
目录号 : GC19092
A dual inhibitor of Aurora kinases and FLT3
Cas No.:1402709-93-6
Sample solution is provided at 25 µL, 10mM.
CCT241736 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 (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 uM), the human FLT3-ITD positive AML cell lines MOLM-13 (GI50, 0.104 uM) and MV4-11 (GI50, 0.291 uM). CCT241736 also inhibits both the autophosphorylation of Aurora-A at T288 (a biomarker for Aurora-A inhibition: IC50, 0.030 uM) and histone H3 phosphorylation at S10 (a biomarker for Aurora-B inhibition: IC50, 0.148 uM), 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[1].
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[1].
References:
[1]. Bavetsias V, et al. Optimization of imidazo[4,5-b]pyridine-based kinase inhibitors: identification of a dual FLT3/Aurora kinase inhibitor as an orally bioavailable preclinical development candidate for the treatment of acute myeloid leukemia. J Med Chem. 2012 Oct 25;55(20):8721-34.
Animal experiment: | Mice[1]Female adult CrTacNCr-Fox1(nu) athymic mice are implanted subcutaneously with 107 FLT3-ITD-positive MV4-11 human leukemia cells. When the tumor xenografts are well-established (10 days after implantation, mean tumor volumes of at least 100 mm3), animals are treated with either vehicle (10% DMSO, 20% PEG 400, 5% Tween 80 and 65% water) or CCT241736 administered orally at two doses, 50 and 100 mg/kg (n = 5 per group). Dosing is twice daily for 7 days, and once daily for a further 4 days[1]. |
References: [1]. Bavetsias V, et al. Optimization of imidazo[4,5-b]pyridine-based kinase inhibitors: identification of a dual FLT3/Aurora kinase inhibitor as an orally bioavailable preclinical development candidate for the treatment of acute myeloid leukemia. J Med Chem. 2012 Oct 25;55(20):8721-34. |
Cas No. | 1402709-93-6 | SDF | |
Canonical SMILES | CC1=NN(C)C=C1C2=NC3=C(N4CCN(CC5=CC=C(Cl)C=C5)CC4)C(Cl)=CN=C3N2 | ||
分子式 | C22H23Cl2N7 | 分子量 | 456.37 |
溶解度 | DMSO : 75 mg/mL (164.34 mM);Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg |
1 mM | 2.1912 mL | 10.956 mL | 21.912 mL |
5 mM | 0.4382 mL | 2.1912 mL | 4.3824 mL |
10 mM | 0.2191 mL | 1.0956 mL | 2.1912 mL |
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2.
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