儿科临床前试验计划对新型 mTOR 激酶抑制剂 MLN0128 的初步测试（第一阶段）。
Initial testing (stage 1) of the investigational mTOR kinase inhibitor MLN0128 by the pediatric preclinical testing program.
机构信息
Texas Tech University Health Sciences Center, Lubbock, Texas.
出版信息
Pediatr Blood Cancer. 2014 Aug;61(8):1486-9. doi: 10.1002/pbc.24989. Epub 2014 Feb 20.
Abstract
MLN0128 is an investigational small molecule ATP-competitive inhibitor of the serine/threonine kinase mTOR. MLN0128 was tested against the in vitro panel at concentrations ranging from 0.1 nM to 1 μM and against the PPTP in vivo panels at a dose of 1 mg/kg administered orally daily × 28. In vitro the median relative IC(50) concentration was 19 nM. In vivo MLN0128 induced significant differences in EFS in 24/31 (77%) solid tumor models, but 0/7 ALL xenografts. The modest activity observed for MLN0128 against the PPTP preclinical models is similar to that previously reported for another TOR kinase inhibitor.
摘要
MLN0128 是一种新型小分子 ATP 竞争性抑制剂，可抑制丝氨酸/苏氨酸激酶 mTOR。MLN0128 在体外检测浓度范围为 0.1 nM 至 1 μM，在体内检测浓度为 1 mg/kg，每天口服给药 28 天。体外实验中，其半数相对抑制浓度（IC50）为 19 nM。体内实验中，MLN0128 在 24/31 个（77%）实体瘤模型中显著诱导 EFS 差异，但在 7/7 个 ALL 异种移植瘤模型中无显著诱导 EFS 差异。MLN0128 对 PPTP 临床前模型的活性与另一种 TOR 激酶抑制剂的活性相似。
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