オザニモド 化学特性,用途語,生産方法
効能
消化性潰瘍薬, スフィンゴシン一リン酸受容体調節薬
説明
Ozanimod is a sphingosine-1-phosphate receptor 1 (S1P
1) and S1P
5 agonist. It induces GTPγS binding in cell membranes expressing human S1P
1 or S1P
5 (EC
50s = 0.41 and 11 nM, respectively) but not cell membranes expressing S1P
2 or S1P
3 receptors (EC
50s = >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.
使用
Ozanimod is an agonist that binds to S1P1 and S1P5 receptors. Experiments on rodents revealed that Ozanimod is effective against autoimmune diseases.
酵素阻害剤
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.
オザニモド 上流と下流の製品情報
原材料
準備製品