pnh

Iptacopan hydrochloride (LNP023 hydrochloride) is an orally bioavailable, highly potent and highly selective factor B inhibitor with an IC50 of 10 nM. Iptacopan hydrochloride shows direct, reversible, and high-affinity binding to human factor B with a KD of 7.9 nM.

Pelecopan (BCX9930) is a potent, selective, orally active inhibitor of complement factor D (IC50=14.3 nM) that prevents both intravascular and extravascular hemolysis in PNH.

Crovalimab (SKY59; RO7112689) is a novel humanized antibody designed to target C5 in a pH-dependent manner, exhibiting binding affinities (KD) of 15.2 nM and 16.8 μM at pH levels of 7.4 and 5.8, respectively. It also shows high affinity for human FcRn at pH 6.0, with a KD of 17 μM. By blocking C5 cleavage by C5 convertase and inhibiting the activity of a C5 variant (p.Arg885His), Crovalimab effectively prevents the formation of C5b-9 across the classical (CP), lectin (LP), and alternative (AP) complement pathways, highlighting its potential utility in research on paroxysmal nocturnal hemoglobinuria (PNH) and other complement-mediated diseases.

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