molecules of the month

Vertex recently disclosed a CNS-penetrant ELOVL1 inhibitor, in which they described preclinical safety findings in rat and cyno. In this article, they disclose a structurally distinct series which displayed similar ocular toxicity in rat, and skin and CNS toxicities in cyno. A third structurally distinct series (undisclosed) also showed toxicities, suggesting a pharmacological class effect. The remarkable similarity of toxicities despite very structurally different leads is as close to a “smoking gun” for on-target toxicity as you can get, and it is generous of Vertex to share this data with the community. This series of articles will remain useful case studies for target validation and dealing with on-target toxicity for future programs. It is notable that the target organs in…