Ponesimod

Relative to the potency of S1P, the potency of ponesimod at human recombinant receptors was 4.4-fold higher for S1P1 and 150-fold lower for human S1P3. Therefore, ponesimod was ∼650-fold more selective for human S1P1 over S1P3 than the natural ligand^[1].

Ponesimod is a new, potent, and selective S1P1 receptor agonist with pharmacokinetic properties allowing rapid restoration of lymphocyte count in peripheral blood upon discontinuation. Ponesimod prevents edema formation, inflammatory cell accumulation, and cytokine release in the skin of mice with delayed-type hypersensitivity. Ponesimod also prevents the increase in paw volume and joint inflammation in rats with adjuvant-induced arthritis. Selective activation of S1P1 using ponesimod leads to blood lymphocyte count reduction and prevention in models of lymphocyte-mediated tissue inflammation. It has the potential to be as effective in animal models of autoimmunity and human autoimmune disease via its effect on T and B cell blood count. Thus, ponesimod may represent a new therapeutic option for the treatment of autoimmune diseases^[1].

Ponesimod is eliminated within 1 week of discontinuation and its pharmacological effects are rapidly reversible ^[2].

• GTPγS Binding Assay

  GTPγS binding assays use membrane preparations of cells expressing recombinant S1P receptors of human, rat, or mouse origin. EC50 values were determined using IC50 Witch. Results were expressed as EC50 using the maximal response generated by S1P (percentage effect of maximal response) as an external maximum and solvent as minimum. Data are expressed as nanomoles of EC50 (geometric mean, geometric standard deviation).

• Animal Models

  Male Wistar rats; Female BALB/c mice

• Dosages

  5 to 10 ml/kg(Rats); 5 ml/kg(Mice)

• Administration

  Oral administration