Therapeutics: Sphingosine 1-phosphate receptor 1 (S1PR1; S1P1; EDG1)

In vitro, rat and mouse studies identified an S1PR1 agonist that could help treat MS and RA. Chemical synthesis and testing in in vitro assays of isoxazole analogs identified a compound, BMS-520, that agonized S1PR1 with an EC50 of 0.47 nM and was 3,400-fold selective for S1PR1 over S1PR3 (S1P3; EDG3). In the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, BMS-520 decreased spinal cord inflammation and demyelination compared with vehicle. In a rat model of RA, BMS-520 decreased paw swelling. Next steps by Bristol-Myers Squibb Co. could include testing BMS-520 in models of other autoimmune diseases.

Celgene Corp. has ozanimod, a selective S1PR1 and S1PR5 (EDG8; S1P5) modulator, in Phase III testing for relapsing-remitting MS (RRMS) and Phase II testing for Crohn's disease and inflammatory bowel disease (IBD)...