CZ415, a Highly Selective mTOR Inhibitor Showing in Vivo Efficacy in a Collagen Induced Arthritis Model
CZ415, a Highly Selective mTOR Inhibitor Showing in Vivo Efficacy in a Collagen Induced Arthritis Model
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DOI：
10.1021/acsmedchemlett.6b00149
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发表时间：
2016-08-01
影响因子：
4.2
通讯作者：
Bergamini, Giovanna
中科院分区：
文献类型：
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作者：
Cansfield, Andrew D.;Ladduwahetty, Tammy;Bergamini, Giovanna
CZ 415是一种有效的ATP竞争性mTOR抑制剂，对任何其他激酶具有前所未有的选择性。除了全面表征其在体外的活动，在体外ADME，并在体内药代动力学数据的报告。在监测mTOR近端下游磷酸化信号传导的机制小鼠模型中证明了这种抑制剂用于研究体内mTOR生物学的适用性。此外，本文报道的化合物是第一个描述在半治疗性胶原诱导的关节炎（CIA）小鼠模型中显示功效的ATP竞争性mTOR抑制剂。
CZ415, a potent ATP-competitive mTOR inhibitor with unprecedented selectivity over any other kinase is described. In addition to a comprehensive characterization of its activities in vitro, in vitro ADME, and in vivo pharmacokinetic data are reported. The suitability of this inhibitor for studying in vivo mTOR biology is demonstrated in a mechanistic mouse model monitoring mTOR proximal downstream phosphorylation signaling. Furthermore, the compound reported here is the first ATP-competitive mTOR inhibitor described to show efficacy in a semitherapeutic collagen induced arthritis (CIA) mouse model.