Complement factor D-IN-1 is a potent and selective small-molecule reversible factor d inhibitor, with IC50s of 0.006 and 0.05 μM in FD Thioesterolytic Fluorescent Assay and a MAC Deposition Assay, respectively.
The highly specific S1 serine protease factor D (FD) plays a central role in the amplification of the complement alternative pathway (AP) of the innate immune system. Complement factor D-IN-1 (compound 2) shows similar potency against human and monkey FD (IC50s in FD thioesterolytic assays of 0.005 μM and in 50% serum MAC deposition assays of 0.011 μM for both human and monkey)[1].
Complement factor D-IN-1 displays an excellent oral PK profile in Sprague-Dawley rats and, following an oral dose (10 mg/kg) in Brown Norway rats, demonstrates a good distribution and sustained exposure in ocular tissues including the neural retina and the posterior eye cup (PEC), which comprises the sclera, retinal pigmented epithelium, and choroid. Mean exposure levels in plasma, the PEC, and the retina at 6 h after dosing are 0.36, 0.43, and 0.09 μM, respectively[1].
[1]. Lorthiois E, et al. Discovery of Highly Potent and Selective Small-Molecule Reversible Factor D InhibitorsDemonstrating Alternative Complement Pathway Inhibition in Vivo. J Med Chem. 2017 Jul 13;60(13):5717-5735.