S1PR5 Agonist

Siponimod (BAF-312) is an orally active, blood-brain barrier penetrant dual agonist of S1P1/S1P5, with EC₅₀ values of 0.39 nM and 0.98 nM, respectively. Siponimod induces S1P1 internalization, activates GIRK channels, inhibits lymphocyte egress, reduces peripheral lymphocyte counts, triggers transient bradycardia, prevents synaptic neurodegeneration, promotes remyelination, alleviates demyelination, and prevents the loss of GABAergic interneurons. Siponimod can be used in research related to multiple sclerosis.

Ozanimod (RPC-1063) is a CNS-penetrant sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity selectively to S1P receptor subtypes 1 (S1P1) and 5 (S1P5). Ozanimod has modulate effect for hS1P₁ and hS1P₅ receptor with EC₅₀s of 1.03 nM and 8.6 nM, respectively. Ozanimod can be used for the research of relapsing multiple sclerosis (MS).

Ponesimod (ACT-128800) is a potent, selective and orally active agonist of S1P₁, with an IC₅₀ of 6 nM in a radioligand binding assay. Ponesimod activates S1P₁-mediated signal transduction with high potency (EC₅₀=5.7 nM). Ponesimod can protect against lymphocyte-mediated tissue inflammation.

CYM-5478 is a potent and highly selective S1P₂ agonist with an EC₅₀ of 119 nM in a TGFα-shedding assay. CYM-5478 protects neural-derived cell lines against Cisplatin toxicity.

AMG 369 is an orally active and potent dual S1P₁/S1P₅ agonist with limited activity at S1P₃ and no activity at S1P₂/S1P₄. AMG 369 reduces blood lymphocyte counts. AMG 369 delays onset and reduces severity of experimental autoimmune encephalomyelitis in rat.

Cenerimod (ACT-334441) is a potent, selective and orally active S1P1 receptor modulator, with an EC₅₀ of 1 nM. Cenerimod shows more than 36 fold selctivity for hS1P1 over hS1P2, hS1P3, hS1P4, and hS1P5 receptor subtypes (EC₅₀s=>10000, 228, 2134, and 36 nM, respectively). Cenerimod can attenuate murine experimental autoimmune encephalomyelitis (EAE) and murine sclerodermatous.

RP101988, the major active metabolite of Ozanimod, is a selective, potent S1PR1 (sphingosine-1-phosphate receptor 1) agonist, with EC₅₀s of 0.19 nM and 32.8 nM for S1PR1 and S1PR5, respectivlely.

Siponimod (BAF-312) hemifumarate is an orally active, blood-brain barrier penetrant dual agonist of S1P1/S1P5, with EC₅₀ values of 0.39 nM and 0.98 nM, respectively. Siponimod hemifumarate induces S1P1 internalization, activates GIRK channels, inhibits lymphocyte egress, reduces peripheral lymphocyte counts, triggers transient bradycardia, prevents synaptic neurodegeneration, promotes remyelination, alleviates demyelination, and prevents the loss of GABAergic interneurons. Siponimod hemifumarate can be used in research related to multiple sclerosis.

RP101075, an active metabolite of Ozanimod, is a potent, orally active S1PR (sphingosine-1-phosphate receptor 1) agonist, with an EC₅₀ of 0.27 nM. RP101075 displays >100-fold selectivity over S1PR5 (EC₅₀=5.9 nM) and >10000-fold over S1PR 2, 3, and 4. RP101075 displays superior cardiovascular safety profile.

S1p receptor agonist 2 (compound 1) is an agonist of S1P5 receptor, exhibits selectivity over the S1P1 and/or S1P3 receptors. S1p receptor agonist 2 can be used for endogenous SIP signaling system research, and alleviating or preventing CNS disorders research, such as neurodegenerative disorders.

S1P5 receptor agonist-1 (Example 6) is an effective and selective S1P5 receptor (S1P5 receptor) agonist. The EC50 values for S1P5 and S1P1 receptors are 20 nM and > 3 μM, respectively. S1P5 receptor agonist-1 can be used in studies on neuroprotection and immune regulation.

RP101442, an active metabolite of Ozanimod, is a selective, potent S1PR1 (sphingosine-1-phosphate receptor 1) agonist, with EC₅₀s of 2.6 nM and 171 nM for S1PR1 and S1PR5, respectively.