Abstract
Scientists at the drugmaker Sanofi have identified a small molecule that can cross the blood-brain barrier and inhibit colony stimulating factor-1 receptor (CSF1R), a kinase that has been linked to multiple sclerosis (MS). The compound, known as RA03546849, is effective at treating MS in rodents. During a talk at the ACS Spring 2023 meeting last week, Andrew A. Scholte, a principal scientist at Sanofi, walked attendees through the campaign that produced the inhibitor. The Sanofi researchers, who were led by Nellwyn Hagan and John L. Kane Jr., hypothesized that by inhibiting CSF1R, they could dampen the effects of microglia and infiltrating macrophages, which are cells in the central nervous system associated with inflammation and other hallmarks of MS. The challenge, Scholte said, was to find a molecule that could cross into the brain and could inhibit CSF1R without also inhibiting other kinases, particularly tropomyosin-related kinases that are abundant in the
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