Initial testing (stage 1) of the investigational mTOR kinase inhibitor MLN0128 by the pediatric preclinical testing program
Initial testing (stage 1) of the investigational mTOR kinase inhibitor MLN0128 by the pediatric preclinical testing program
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DOI：
10.1002/pbc.24989
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发表时间：
2014-08-01
影响因子：
3.2
通讯作者：
Smith, Malcolm A.
中科院分区：
文献类型：
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作者：
Kang, Min H.;Reynolds, C. Patrick;Smith, Malcolm A.
MLN0128是一种正在研究的丝氨酸/苏氨酸激酶mTOR的小分子atp竞争性抑制剂。MLN0128以0.1nM至1M的浓度对体外组和1mg/kg的每日口服剂量对PPTP体内组进行了实验。体外IC50的中位相对浓度为19nM。在体内，MLN0128在24/31（77%）实体瘤模型中诱导了显著的EFS差异，但在ALL异种移植物中却有0/7。MLN0128对PPTP临床前模型的适度活性与先前报道的另一种TOR激酶抑制剂相似。儿科血癌2014；61:1486 - 1489。(c) 2014 Wiley期刊公司
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 0.1nM to 1M and against the PPTP in vivo panels at a dose of 1mg/kg administered orally dailyx28. In vitro the median relative IC50 concentration was 19nM. 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. Pediatr Blood Cancer 2014; 61:1486-1489. (c) 2014 Wiley Periodicals, Inc.