oral interleukin 17A modulator
favorable in vivo PK profile in multiple species
from a previous patent and SBDD
J. Med. Chem.
LEO Pharma Research & Early Development, Ballerup, DK
Context. “Compound 23” (LEO Pharma) is an oral IL-17A protein−protein interaction modulator being developed for psoriasis and other inflammatory diseases. Like most cytokines, the involvement of IL-17A in chronic inflammatory diseases has been well-researched. IL-17A is the key cytokine that mediates psoriasis, and targeting it or its receptor has led to the approval of the highly effective monoclonal antibodies secukinumab (Cosentyx), ixekizumab (Taltz), and brodalumab (Siliq) by the FDA and EMA, and bimekizumab (Bimzelx) by the EMA. Owing to the phenomenon of biologic fatigue caused by anti-drug antibodies, which has been associated with anti-psoriatic antibody treatment, oral small molecule inhibitors with similar efficacy and safety have been explored as an alternative therapy. However, modulating protein-protein interactions (PPIs) with small molecules,…