molecules of the month

The Deciphera CSF1R kinase inhibitor, vimseltinib (DCC-3014), is a selective oral TKI that induces an inactive conformation of CSF1R by biomimetically nucleating an array of 17 H-bonds in the switch control region of this switch control kinase. Several small and large molecule agents targeting CSF1R have been in development, and a small molecule CSF1R inhibitor (pexidartinib) was approved in 2019. Vimseltinib significantly inhibited CSF1R signaling in PK/PD models at doses as low as 3 mg/kg orally and depletes macrophages in efficacy models. Single agent and combination efficacy with anti-PD1 immunotherapy in a syngeneic mouse colorectal cancer model with effects on the adaptive immune system were also observed, in agreement with the hypothesis that certain macrophages play a role in tumor immune evasion. In…