Global Discovery Chemistry, Novartis Institutes of Biomedical Research, Cambridge, MA, USA.
Chemical Biology and Therapeutics, Novartis Institutes of Biomedical Research, Cambridge, MA, USA.
Nat Chem Biol. 2019 Jul;15(7):666-668. doi: 10.1038/s41589-019-0303-9. Epub 2019 Jun 17.
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.
补体途径是免疫系统的重要组成部分，其不受控制的激活与许多疾病有关。人类补体成分 5 蛋白（C5）是补体途径中的一个已验证的药物靶点，因为抗 C5 抗体（Soliris）是阵发性睡眠性血红蛋白尿症的一种已批准的治疗药物。在这里，我们报告了第一个 C5 补体蛋白小分子抑制剂的鉴定、优化和作用机制。
