Ningetinib Tosylate

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Chemical Structure| 1394820-77-9 同义名 : -
CAS号 : 1394820-77-9
货号 : A671711
分子式 : C38H37FN4O8S
纯度 : 99%+
分子量 : 728.79
MDL号 : MFCD28142839
存储条件：

Pure form Inert atmosphere, room temperature

In solvent -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：
生物活性
描述 Ningetinib Tosylate is the tosylate salt form of Ningetinib. Ningetinib is a potent and multiple-target tyrosine kinase inhibitor with IC50 values of 6.7, 1.9 and < 1.0 nM against c-Met, VEGFR-2 and Axl, as well as tyrosine kinase Mer, and FLT3, all of which have been implicated in tumor pathogenesis. Ningetinib exhibited inhibition of HGF and VEGF-stimulated HUVEC proliferation and microvascular angiogenesis in rat aortic rings with IC50 values of 8.6 and 6.3 nM, respectively. Ningetinib showed good pharmacodynamics as a single oral dose of 3mg/kg Ningetinib potently inhibited the phosphorylation of c-Met and its downstream signaling kinases AKT and ERK1/2 for up to 6 hours in tumor tissues of U87MG tumor-bearing nude mice. Also it displayed excellent oral bioavailability (> 60% across animal species). Ningetinib exhibited antitumor efficacy in various human tumor subcutaneous xenograft models in athymic mice, including Caki-1 (kidney carcinoma), U-87MG (glioblastoma), NCI-H441 (lung adenocarcinoma), MDA-MB-231 (breast adenocarcinoma), SMMC-7721 (hepatoma), 5637 (bladder carcinoma) and SK-OV-3 (ovarian carcinoma), with ED50 values ranging in < 1mg/kg (NCI-H441) to ∼ 6 mg/kg (SMMC-7721). It prolonged the median survival time and yielded significant increase in life-span value (ILS = 32%, p = 0.003) at an oral dose of 20 mg/kg/day (dosed 21 days) in orthotopic U87MG human glioblastoma xenograft model versus the vehicle-treated group[1]. Up to now, a phase I/II study of ningetinib to treat for non-small cell lung cancer, and a phase I to renal cancer and acute myeloid leukaemia are under recruiting (https://clinicaltrials.gov/).
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.37mL

0.27mL

0.14mL

6.86mL

1.37mL

0.69mL

13.72mL

2.74mL

1.37mL
参考文献

[1]Ning X, Yingjun Z, et al. CT053PTSA, a novel c-MET and VEGFR2 inhibitor, potently suppresses angiogenesis and tumor growth. Volume 74, Issue 19 Supplement, pp. 1755.