Озанимод

Ozanimod is a sphingosine-1-phosphate receptor 1 (S1P₁) and S1P₅ agonist. It induces GTPγS binding in cell membranes expressing human S1P₁ or S1P₅ (EC₅₀s = 0.41 and 11 nM, respectively) but not cell membranes expressing S1P₂ or S1P₃ receptors (EC₅₀s = >10,000 nM for both). Ozanimod (0.2 mg/kg) reduces the number of peripheral lymphocytes in rats. It reduces disease severity and the number of circulating lymphocytes in a mouse model of experimental autoimmune encephalomyelitis (EAE). Ozanimod (0.3 and 1 mg/kg) reduces disease severity and body weight loss in a mouse model of TNBS-induced colitis. Formulations containing ozanimod have been used in the treatment of relapsing multiple sclerosis and ulcerative colitis.

Ozanimod is an agonist that binds to S1P1 and S1P5 receptors. Experiments on rodents revealed that Ozanimod is effective against autoimmune diseases.

The most common ozanimod (Zeposia) side effects include colds, headaches, and chest and urinary tract infections. Compared to other disease-modifying therapies, the risk of side effects, especially serious ones, is in the middle and similar to those you get with fingolimod. That said, in trials, ozanimod had fewer side effects than fingolimod. When you take your first dose of the drug, it can cause your heartbeat to slow down (it soon goes back to normal). Because of this, your first dose will be smaller andl gradually increase over the first week. Ozanimod causes a short-lived rise in your liver enzymes. They generally go back to normal levels without you needing to stop taking it.

This orally available S1PR1 modulator (FW = 404.46 g/mol; CAS 1306760- 87-1; Solubility: 81 mg/mL DMSO; < 1 mg/mL H2O), also named RPC1063 and 5-[3-[(1S)-2,3-dihydro-1-[(2-hydroxyethyl)amino]-1H-inden- 4-yl]-1,2,4-oxadiazol-5-yl]-2-(1-methylethoxy)benzonitrile, selectively targets sphingosine 1-Phosphate (S1P) receptors, which mediate multiple processes, including lymphocyte trafficking, cardiac function, and endothelial barrier integrity. Ozanimod is specific for S1P1R (IC50 = 0.4 nM) and S1P5R, inducing S1P1R internalization and reversibly reducing the number of circulating B and CCR7+ T lymphocytes in vivo. It shows high oral bioavailability and volume of distribution, and a circulatory half-life that supports once daily dosing. Oral ozanimod reduced inflammation and disease parameters in three autoimmune disease models, commending its use in the treatment of relapsing multiple sclerosis (RMS) and inflammatory bowel disease (IBD). Indeed, the safety and efficacy of this modulator ozanimod in relapsing multiple sclerosis is indicated on the basis of a randomized, placebo-controlled, Phase 2 trial. Other SIPR1-directed immunomodulators include laquinimod, ponesimod, and siponimod.