包装 | 价格(元) |
5mg | 电议 |
10mg | 电议 |
50mg | 电议 |
100mg | 电议 |
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]. |
产品描述 | 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: |