Ponesimod

SKU: orb1223849

Description

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.

Key Properties

• CAS Number: 854107-55-4
• MW: 460.9736
• Purity: >98% (HPLC)
• Formula: C₂₃H₂₅ClN₂O₄S
• SMILES: O=C1N(C2=CC=CC=C2C)/C(S/C1=C\C3=CC=C(OC[C@H](O)CO)C(Cl)=C3)=N/CCC
• Target: Lysophospholipid Receptor
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  Animal model: Female BALB/c mice (15-25 g) sensitized with DNFB. Dosage: 30 and 175 mg/kg. Administration: Gavage (30 mg/kg) 19 and 3 h before sensitization, followed by administration as food admix (175 mg/kg/day) for 8 days. Result: 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%.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

ACT-128800

Quick Database Links

Gene Symbol

Lysophospholipid Receptor