The first potent inhibitor of mammalian group X secreted phospholipase A2:: Elucidation of sites for enhanced binding
The first potent inhibitor of mammalian group X secreted phospholipase A2:: Elucidation of sites for enhanced binding
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DOI：
10.1021/jm060136t
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发表时间：
2006-05-18
影响因子：
7.3
通讯作者：
Gelb, Michael H.
中科院分区：
文献类型：
--
作者：
Smart, Brian P.;Oslund, Rob C.;Gelb, Michael H.
利用人X组分泌型磷脂酶A（2）（hGX）的X-射线结构，我们进行了吲哚类抑制剂的结构设计，并采用新的合成路线制备了化合物。最有效的化合物抑制hGX和小鼠直系同源物，IC 50为75 nM。该化合物是迄今为止报道的最有效的hGX抑制剂，也被发现抑制其他小鼠和人sPLA（2）的子集。
Using the X-ray structure of human group X secreted phospholipase A(2) (hGX), we carried out structure-based design of indole-based inhibitors and prepared the compounds using a new synthetic route. The most potent compound inhibited hGX and the mouse orthologue with an IC50 of 75 nM. This compound is the most potent hGX inhibitor reported to date and was also found to inhibit a subset of the other mouse and human sPLA(2)s.