ATC Group: L04AE Sphingosine-1-phosphate (S1P) receptor modulators

Etrasimod is a sphingosine-1-phosphate (S1P) receptor modulator that binds to S1P receptors 1, 4 and 5 (S1P_1,4,5) and is a balanced G-protein and beta-arrestin agonist at S1P₁. Etrasimod has minimal activity on S1P₃ and no activity on S1P2. Etrasimod partially and reversibly blocks the capacity of lymphocytes to egress from lymphoid organs, reducing the number of lymphocytes in peripheral blood thereby lowering the number of activated lymphocytes in the tissue. The mechanism by which etrasimod exerts therapeutic effects in ulcerative colitis is unknown but may involve the reduction of lymphocyte migration into sites of inflammation.

Fingolimod is a sphingosine 1-phosphate receptor modulator. Fingolimod is metabolised by sphingosine kinase to the active metabolite fingolimod phosphate. By acting as a functional antagonist of S1P receptors on lymphocytes, fingolimod phosphate blocks the capacity of lymphocytes to egress from lymph nodes, causing a redistribution, rather than depletion, of lymphocytes.

Ozanimod is a sphingosine 1-phosphate (S1P) receptor modulator, which binds selectively to sphingosine 1-phosphate receptor subtypes 1 and 5. Ozanimod causes lymphocyte retention in lymphoid tissues.

Ponesimod is a sphingosine 1-phosphate (S1P) receptor 1 modulator. Ponesimod binds with high affinity to S1P receptor 1 located on lymphocytes. It blocks the capacity of lymphocytes to egress from lymph nodes reducing the number of lymphocytes in peripheral blood. The mechanism by which it exerts therapeutic effects in multiple sclerosis may involve reduction of lymphocyte migration into the central nervous system.

Siponimod is a sphingosine-1-phosphate (S1P) receptor modulator. By acting as a functional antagonist on S1P1 receptors on lymphocytes, siponimod prevents egress from lymph nodes. This reduces the recirculation of T cells into the central nervous system (CNS) to limit central inflammation. Siponimod is indicated for the treatment of adult patients with secondary progressive multiple sclerosis (SPMS) with active disease.