Ponesimod

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的、选择性的、口服活性的 S1P1 受体激动剂，EC50 为 9.1 nM；对 S1P3 表现出弱活性 (EC50=123 nM)。

A potent, selective, orally active S1P1 receptor agonist with EC50 of 9.1 nM; shows weak activity on S1P3 (EC50=123 nM); activates S1P1-mediated signal transduction with high potency (EC50 of 5.7 nM); causes maximal reduction of circulating lymphocytes at a dose of 3 mg/kg.Multiple Sclerosis Phase 3 Clinical(In Vitro):Ponesimod activates human S1P1-5 receptors with EC50s of 5.7, >10000, 105, 1108 and 59.1 nM respectively in GTPγS binding assay.Ponesimod activates S1P1 receptors with EC50s of 5.7, 1.9, and 1.4 nM for human, rat, and mouse S1P receptors respectively.(In Vivo):Ponesimod (30 and 175 mg/kg; once daily p.o. for 8 d) prevents delayed-type hypersensitivity in mice.Ponesimod (30 mg/kg by gavage 3 h before and 6 h after adjuvant injection followed by 100 mg/kg/day by administration as food admix for 18 days) prevents adjuvant-induced arthritis in rats.Ponesimod (0.3-100 mg/kg; a single oral gavage) causes a dose-dependent reduction in lymphocyte count, with a plateau effect being reached at 3 mg/kg in rats.Ponesimod (100 mg/kg; once daily oral gavage for 7 d) results in a lymphocyte count reduction to 1900 lymphocytes/μL, and this effect is maintained over the entire 7 days studies. Lymphocyte count returned to baseline levels within 48 h after discontinuation of dosing.

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Animal Model:Female BALB/c mice (15-25 g) sensitized with DNFBDosage:30 and 175 mg/kgAdministration:Gavage (30 mg/kg) 19 and 3 h before sensitization, followed by administration as food admix (175 mg/kg/day) for 8 daysResult:Caused a 60 to 90% reduction of delayed-type hypersensitivity (DTH) parameters of the skin, such as edema, protein extravasation, and neutrophil myeloperoxidase (MPO) activity.Reduced skin levels of proinflammatory cytokines, such as IL-1β, IL-6, IFNγ, TNFα, and several chemokines to different degrees ranging from -27 to -100%.

ACT-128800

GPCR/G Protein

Lysophospholipid Receptor

S1P1

Inflammation/Immunology

Multiple Sclerosis

854107-55-4

460.9736

C23H25ClN2O4S

>98% (HPLC)

10 mM in DMSO

O=C1N(C2=CC=CC=C2C)/C(S/C1=C\C3=CC=C(OC[C@H](O)CO)C(Cl)=C3)=N/CCC

4-Thiazolidinone, 5-[[3-chloro-4-[(2R)-2,3-dihydroxypropoxy]phenyl]methylene]-3-(2-methylphenyl)-2-(propylimino)-, (2Z,5Z)-

(-20℃)

With Ice Pack

≥ 2 years