The S1P1 receptor, a protein that plays a pivotal role in regulating immune response, interacts with S1P, a plasma lipid mediator. Remarkably, S1P regulates an array of physiological phenomena such as angiogenesis, inflammation, immunity, cell motility, and neurotransmitter release. Therefore, S1PR modulation has emerged an option for patients battling multiple sclerosis, offering an innovative mechanism of selective immune sequestration. For example, the advent of FTY720/Fingolimod, the first nonselective S1P1‐5 receptor modulator, was a breakthrough, demonstrating clinical efficacy in relapsing forms of multiple sclerosis. However, reports of cardiovascular, hepatic, and respiratory side effects highlighted a need for better alternatives. Enter Cenerimod, a novel, potent, and selective S1P1 receptor modulator featuring unique signaling properties, while notably negating broncho‐ and vasoconstrictor effects. Hence, Cenerimod stands as a promising candidate in the quest for improved S1P1 receptor modulators.

Cenerimod is an orally active S1P1 agonist for autoimmune and inflammatory diseases research.

In vitro, Cenerimod has emerged as a highly potent S1P1 receptor agonist. In assays using (³⁵S)-GTPγS and HUVEC cell membrane preparations. It demonstrates an EC₅₀ of just 2 nM. Furthermore, Cenerimod activates the G protein and escalates Ca²⁺ signaling in CHO cells, with EC₅₀s of 1 nM and 124 nM respectively. In an intriguing turn of events, Cenerimod (5 μM, 24 h) effectively inhibits collagen production in fibroblasts.

In vivo, with a single oral dose of 0.1-10 mg/kg, Cenerimod shows its capabilities by reversibly reducing the number of circulating lymphocytes in rats. Besides, Cenerimod (6 mg/kg, p.o., daily for 30 days) remarkably attenuates disease symptoms in an experimental autoimmune encephalitis (EAE) mouse model. Moreover, Cenerimod (10 mg/kg/day, 42 days) effectively attenuates skin and lung fibrosis in Scl-cGVHD mice.

In summary, Cenerimod effectively modulates the function of S1P1 receptor. Cenerimod influences the movement of lymphocytes – a key factor in the progression of autoimmune.

References:

[1]. Piali L, et, al. Cenerimod, a novel selective S1P 1 receptor modulator with unique signaling properties. Pharmacol Res Perspect. 2017 Dec;5(6):e00370.

[2]. Kano M, et, al. Attenuation of murine sclerodermatous models by the selective S1P 1 receptor modulator cenerimod. Sci Rep. 2019 Jan 24;9(1):658.