title: Structure-Guided Design of Novel, Potent, and Selective Macrocyclic Plasma Kallikrein Inhibitors.
abstract: A 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 inhibitor29, with an IC50of 2 nM for one olefinic isomer and 42.3 nM for the other olefinic isomer.
authors.affiliation: Global Blood Therapeutics , South San Francisco, California 94080, United States.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Li
authors.affiliation: Global Blood Therapeutics , South San Francisco, California 94080, United States.
authors.forename: James
authors.initials: J
authors.lastname: Partridge
authors.affiliation: Global Blood Therapeutics , South San Francisco, California 94080, United States.
authors.forename: Abel
authors.initials: A
authors.lastname: Silva-Garcia
authors.affiliation: Global Blood Therapeutics , South San Francisco, California 94080, United States.
authors.forename: Peter
authors.initials: P
authors.lastname: Rademacher
authors.affiliation: Global Blood Therapeutics , South San Francisco, California 94080, United States.
authors.forename: Andreas
authors.initials: A
authors.lastname: Betz
authors.affiliation: Global Blood Therapeutics , South San Francisco, California 94080, United States.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Global Blood Therapeutics , South San Francisco, California 94080, United States.
authors.forename: Hing
authors.initials: H
authors.lastname: Sham
authors.affiliation: Pharmaron Xi'an Co. , Xi'an, Shaanxi 710018, China.
authors.forename: Yunjin
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Pharmaron Xi'an Co. , Xi'an, Shaanxi 710018, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Shan
authors.affiliation: Pharmaron Xi'an Co. , Xi'an, Shaanxi 710018, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Pharmaron Xi'an Co. , Xi'an, Shaanxi 710018, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Pharmaron Xi'an Co. , Xi'an, Shaanxi 710018, China.
authors.forename: Haijuan
authors.initials: H
authors.lastname: Shi
authors.affiliation: Pharmaron Xi'an Co. , Xi'an, Shaanxi 710018, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Pharmaron Xi'an Co. , Xi'an, Shaanxi 710018, China.
authors.forename: Xubo
authors.initials: X
authors.lastname: Ma
authors.affiliation: Pharmaron Xi'an Co. , Xi'an, Shaanxi 710018, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
keywords: Hereditary angioedema; macrocycle; plasma kallikrein; protease inhibitor; structure-based design