Cenerimod, a novel selective S1P1 receptor modulator with unique signaling properties.

Pharmacology research & perspectives 2017 Dec

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Sphingosine-1-phosphate receptor 1 (S1P1 ) modulators sequester circulating lymphocytes within lymph nodes, thereby preventing potentially pathogenic autoimmune cells from exiting into the blood stream and reaching inflamed tissues. S1P1 receptor modulation may thus offer potential to treat various autoimmune diseases. The first nonselective S1P1-5 receptor modulator FTY720/fingolimod/Gilenya® has successfully demonstrated clinical efficacy in relapsing forms of multiple sclerosis. However, cardiovascular, hepatic, and respiratory side-effects were reported and there is a need for novel S1P1 receptor modulators with better safety profiles. Here, we describe the discovery of cenerimod, a novel, potent and selective S1P1 receptor modulator with unique S1P1 receptor signaling properties and absence of broncho- and vasoconstrictor effects ex vivo and in vivo. Cenerimod dose-dependently lowered circulating lymphocyte counts in rats and mice after oral administration and effectively attenuated disease parameters in a mouse experimental autoimmune encephalitis (EAE) model. Cenerimod has potential as novel therapy with improved safety profile for autoimmune diseases with high unmet medical need. © 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.

Citation

Luca Piali, Magdalena Birker-Robaczewska, Cyrille Lescop, Sylvie Froidevaux, Nicole Schmitz, Keith Morrison, Christopher Kohl, Markus Rey, Rolf Studer, Enrico Vezzali, Patrick Hess, Martine Clozel, Beat Steiner, Martin H Bolli, Oliver Nayler. Cenerimod, a novel selective S1P1 receptor modulator with unique signaling properties. Pharmacology research & perspectives. 2017 Dec;5(6)