Ensemble has used its DNA-programmed chemistry platform to identify a series of unique small molecule macrocycles that are potent antagonists of Interleukin-17 (IL-17). IL-17 is a pro-inflammatory cytokine implicated in multiple inflammatory and autoimmune diseases such as psoriasis, rheumatoid arthritis, Crohn’s and inflammatory bowel disease.
Using traditional medicinal chemistry, the initial macrocyclic hit compounds were optimized to produce potent and selective small molecules, which represent first-in-class nanomolar antagonists of this clinically validated protein-protein-interaction target. In the past, IL-17 has proven intractable to traditional small molecule pharmaceutical approaches and has only been addressed with antibody therapeutics. A small, orally-active inhibitor of IL-17 would have significant delivery and therapeutic advantages over the current class of anti-IL-17 antibody products.
This program has been licensed to Novartis.