S1PR1 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).

SEW2871 is an orally active, potent, highly selective S1P1 (sphingosine-1-phosphate type 1 receptor) agonist, with an EC₅₀ of 13.8 nM. SEW2871 activates ERK, Akt, and Rac signaling pathways and induces S1P1 internalization and recycling. SEW2871 reduces lymphocyte numbers in blood. SEW2871 can be used for the research of diabetes, Alzheimer’s disease, liver fibrosis, and inflammatory responses.

SAR247799 (S1P1 agonist 3) is an oral activity, selective G-protein-biased sphingosine-1 phosphate receptor-1 (S1P1 ) agonist, with EC₅₀s rang from 12.6 to 493 nM in S1P1-overexpressing cells and HUVECs. SAR247799 can be used for the research of endothelial protection, including type-2 diabetes, metabolic syndrome.

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.

PF-462991 (PF-991) is a S1P1 receptor agonist with an EC₅₀ of 1.9 nM. PF-462991 functionally activates this receptor via the β-arrestin pathway. PF-462991 is applicable to research related to rheumatoid arthritis.

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.

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.

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.

IMMH001, also called SYL930, is an orally active, potent and selective S1P1 (sphingosine-1-phosphate receptor 1) agonist. IMMH001 decreased levels of both chemokines and proinflammatory cytokines, including IL-1β, IL-5, IL-18, IP10, CCL3, and CCL5. IMMH001 can be used for rheumatoid arthritis (RA) research.

L-threo Lysosphingomyelin (d18:1) (L-threo-Sphingosylphosphorylcholine) is an endogenous bioactive sphingolipid. L-threo Lysosphingomyelin (d18:1) is a potent S1P receptor agonist with EC₅₀s of 19.3, 131.8, and 313.3 nM for hS1P₁, hS1P₃, and hS1P₂, respectively.

Vibozilimod (SCD-044) is an oral S1P1/EDG1 receptor-selective agonist with an EC₅₀ of <1 nM. Vibozilimod promotes S1P1/EDG1 receptor internalization, inhibits lymphocyte migration, induces lymphopenia and reduces lymphocyte counts. Vibozilimod is used for the research of inflammatory diseases such as psoriasis and atopic dermatitis.

S1PR1 agonist 3 (Compound Y18) is a highly selective S1PR1 receptor agonist (EC₅₀=0.98 nM). S1PR1 agonist 3 is promising for research of autoimmune diseases such as multiple sclerosis and ulcerative colitis.

BMS-520 is a potent, orally active and selective sphingosine-1-phosphate 1 (S1P₁) agonist with an EC₅₀ of 0.47nM. BMS-520 shows ~3400-fold selectivity over S1P₃. BMS-520 demonstrates impressive efficacy in a rat model of arthritis and in a mouse experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. BMS-520 can be used for arthritis and EAE research.

TC-SP 14 (compound 14) is an orally active and potent S1P1 agonist (EC₅₀ = 0.042 μM) with minimal activity at S1P3 (EC₅₀ = 3.47 μM). TC-SP 14 significantly reduces blood lymphocyte counts and attenuates a delayed type hypersensitivity (DTH) response to antigen challenge.

TYY-31 is an orally active, selective S1PR1 agonist with an EC₅₀ of 1.13 pM. TYY-31 promotes the phosphorylation of ERK1/2. TYY-31 exerts anti-inflammatory and immunosuppressive effects, ameliorates DSS-induced colitis in mice, and reduces peripheral blood lymphocyte counts in mice in a dose-dependent manner. TYY-31 can be used for the research of ulcerative colitis.

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.