A small-molecule inhibitor of C5 complement protein

被引：13

作者：

Jendza, Keith ^{[1
]}

Kato, Mitsunori ^{[1
]}

Salcius, Michael ^{[2
]}

Srinivas, Honnappa ^{[3
]}

De Erkenez, Andrea ^{[4
]}

Nguyen, Anh ^{[4
]}

McLaughlin, Doug ^{[2
]}

Be, Celine ^{[3
]}

Wiesmann, Christian ^{[3
]}

Murphy, Jason ^{[2
]}

Bolduc, Philippe ^{[1
]}

Mogi, Muneto ^{[1
]}

Duca, Jose ^{[1
]}

Namil, Abdel ^{[1
]}

Capparelli, Michael ^{[1
]}

Darsigny, Veronique ^{[1
]}

Meredith, Erik ^{[1
]}

Tichkule, Ritesh ^{[1
]}

Ferrara, Luciana ^{[4
]}

Heyder, Jessica ^{[4
]}

Liu, Fang ^{[4
]}

Horton, Patricia A. ^{[2
]}

Romanowski, Michael J. ^{[2
]}

Schirle, Markus ^{[2
]}

Mainolfi, Nello ^{[1
]}

Anderson, Karen ^{[4
]}

Michaud, Gregory A. ^{[2
]}

机构：

[1] Novartis Inst Biomed Res, Global Discovery Chem, Cambridge, MA USA

[2] Novartis Inst Biomed Res, Chem Biol & Therapeut, Cambridge, MA 02139 USA

[3] Novartis Inst Biomed Res, Chem Biol & Therapeut, Basel, Switzerland

[4] Novartis Inst Biomed Res, Ophthalmol, Cambridge, MA USA

来源：

NATURE CHEMICAL BIOLOGY | 2019年 / 15卷 / 07期

关键词：

SYSTEM;

D O I：

10.1038/s41589-019-0303-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The complement pathway is an important part of the immune system, and uncontrolled activation is implicated in many diseases. The human complement component 5 protein (C5) is a validated drug target within the complement pathway, as an anti-C5 antibody (Soliris) is an approved therapy for paroxysmal nocturnal hemoglobinuria. Here, we report the identification, optimization and mechanism of action for the first small-molecule inhibitor of C5 complement protein.

引用

页码：666 / +

页数：5

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