ml6b00384_si_001.pdf (2.03 MB)
Structure-Guided Design of Novel, Potent, and Selective Macrocyclic Plasma Kallikrein Inhibitors
journal contribution
posted on 2016-12-06, 00:00 authored by Zhe Li, James Partridge, Abel Silva-Garcia, Peter Rademacher, Andreas Betz, Qing Xu, Hing Sham, Yunjin Hu, Yuqing Shan, Bin Liu, Ying Zhang, Haijuan Shi, Qiong Xu, Xubo Ma, Li ZhangA series of macrocyclic
analogues were designed and synthesized
based on the cocrystal structure of small molecule plasma kallikrein
(pKal) inhibitor, 2, with the pKal protease domain. This
led to the discovery of a potent macrocyclic pKal inhibitor 29, with an IC50 of 2 nM for one olefinic isomer
and 42.3 nM for the other olefinic isomer.