通过解构和再生方法发现强效、高效和选择性的磷酸肌醇 3-激酶 δ 抑制剂。
Discovery of Potent, Efficient, and Selective Inhibitors of Phosphoinositide 3-Kinase δ through a Deconstruction and Regrowth Approach.
机构信息
GlaxoSmithKline R&D, Medicines Research Centre , Gunnels Wood Road , SG1 2NY Stevenage , U.K.
出版信息
J Med Chem. 2018 Dec 27;61(24):11061-11073. doi: 10.1021/acs.jmedchem.8b01556. Epub 2018 Dec 21.
PMID:30532965
Abstract
A deconstruction of previously reported phosphoinositide 3-kinase δ (PI3Kδ) inhibitors and subsequent regrowth led to the identification of a privileged fragment for PI3Kδ, which was exploited to deliver a potent, efficient, and selective lead series with a novel binding mode observed in the PI3Kδ crystal structure.
摘要
对先前报道的磷酸肌醇 3-激酶 δ（PI3Kδ）抑制剂进行解构，随后重新生长，从而确定了 PI3Kδ 的一个特权片段，该片段被用于开发一种有效的、选择性的先导化合物系列，在 PI3Kδ 的晶体结构中观察到了一种新的结合模式。
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