Agonists of sphingosine-1-phosphate receptor 1 (S1P1) have demonstrated utility in the treatment of several autoimmune disorders in clinical trials, and in clinical practice for relapsing-remitting multiple sclerosis.  However, several safety concerns have also been associated with full agonism at this receptor.  For example, pulmonary edema was noted in preclinical toxicity studies, while cardiovascular effects in humans are now thought to be mediated by S1P1 activation.  In contrast to earlier examples within the field, our team has pursued next-generation modulators of S1P1 that exhibit ligand-biased signaling as a means to dissociate the desired efficacy from the undesired effects.  The optimization of partial agonists of S1P1 leading to the identification of clinical compound BMS-986166 will be described.   <br/>

Optimization of S1P1 partial agonists leading to the identification of BMS-986166

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.