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Overview
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Background
BAF312 is a potent and selective agonist of S1P with EC50 value of 0.39nM for S1P1 receptors and 0.98nM for S1P5 receptors, respectively [1].
BAF312 has shown >1000-fold selectivity for S1P1 versus S1P2, S1P3 and S1P4 receptors [1]. In vitro metabolism studies with liver microsomes have shown that the metabolic clearance of BAF312 is high in rat, low to moderate in monkey and human being, and low in dog and mouse. Moreover, BAF312 has been revealed to dose-dependently reduce peripheral lymphocyte counts in Lewis rats [2].
.[1] Gergely P1, Nuesslein-Hildesheim B, Guerini D, Brinkmann V, Traebert M, Bruns C, Pan S, Gray NS, Hinterding K, Cooke NG, Groenewegen A, Vitaliti A, Sing T, Luttringer O, Yang J, Gardin A, Wang N, Crumb WJ Jr, Saltzman M, Rosenberg M, Wallström E. The selective sphingosine 1-phosphate receptor modulator BAF312 redirects lymphocyte distribution and has species-specific effects on heart rate. Br J Pharmacol. 2012 Nov;167(5):1035-47.
[2] Pan S1, Gray NS1, Gao W1, Mi Y1, Fan Y1, Wang X1, Tuntland T1, Che J1, Lefebvre S1, Chen Y1, Chu A1, Hinterding K2, Gardin A2, End P2, Heining P2, Bruns C2, Cooke NG2, Nuesslein-Hildesheim B2 .Discovery of BAF312 (Siponimod), a Potent and Selective S1P Receptor Modulator. ACS Med Chem Lett. 2013 Jan 4;4(3):333-7.
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