Figure 11.

Complement inhibitors target different levels and steps of the complement cascade. Complement inhibitors which are evaluated in clinical trials for various kidney diseases bind to different complement proteins and inhibit the cascade at different levels. C1 inhibitor binds to C1 and blocks C1 activation. OMS 721 binds to the lectin pathway protease MASP2. C3 targeting proteins include APL2 (Apellis) and AMY 101 (Amyndas). The Factor D inhibitor ACH-4471 (Achillion) binds to Factor D, a protease which cleaves in its active state Factor B. LPN023 (Novartis) a small Factor B binding protein blocks formation of the enzymatically active AP C3 Convertase. Several compounds target complement at the level of C5. Eculizumab, and the new version Ravulizumab (both Alexion) bind to C5 and block activation of the protein. Coversin is a tick derived C5 binding protein (Akari) and C5 inhibitor. C5 synthesis is blocked by Cemdisiran as an RNAi targeted strategy (Alnylam), and by LFG-316 (Novartis). The complement inflammatory C5a—C5aR1 axis is inhibited by IFX-1 (InflaRx) and Avacopan (Chemocentryx).