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Danicopan (ACH-4471), a selective and orally active small-molecule factor D inhibitor, shows high binding affinity to human Factor D with Kd value of 0.54 nM. Danicopan (ACH-4471) inhibits alternative pathway of complement (APC) activity, has potential to block the alternative pathway of complement in paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS)[1].

Danicopan (ACH-4471) inhibits the proteolytic activity of purified Factor D against its natural substrate Factor B in complex with C3b, blocking production of Bb fragment in a dose-dependent manner with an IC50 value of 0.015 μM[1].Danicopan (ACH-4471)potently inhibits hemolysis with IC50 values ranging from 0.0040 μM to 0.027 μM (IC90 values from 0.015 μM to 0.11 μM) [1].

[1]. Yuan X, et al. Small-molecule factor D inhibitors selectively block the alternative pathway of complement in paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. Haematologica. 2017 Mar;102(3):466-475..
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