LPL Receptor Agonist

CS-2100 (Compound 10b) is a potent, selective, orally active and S1P₃-sparing S1P₁ agonist with an EC₅₀ of 4.0 nM for human S1P₁. CS-2100 shows in vivo immunosuppressive efficacy in rats with an ID₅₀ (infective dose) of 0.407 mg/kg for HvGR.

S1P1 agonist III is an orally active hS1P1 agonist with an EC₅₀ value of 18 nM. S1P1 agonist III shows limited activity against hS1P3. S1P1 agonist III can be used in the research of multiple sclerosis.

ASP-4058 hydrochloride is a next-generation, selective and orally active agonist for Sphingosine 1-Phosphate receptors 1 and 5 (S1P₁ and S1P₅), ameliorates rodent experimental autoimmune encephalomyelitis with a favorable safety profile.

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.

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.

CYM5442 hydrochloride is a potent, highly-selective and orally active sphingosine 1-phosphate (S1P1) receptor agonist with an EC₅₀ of 1.35 nM. CYM5442 hydrochloride is inactive against S1P2, S1P3, S1P4, and S1P5. CYM5442 hydrochloride activates S1P1-dependent p42/p44-MAPK phosphorylation. CYM5442 exerts retinal neuroprotection. CYM5442 hydrochloride can easily penetrate the central nervous system (CNS).

ASP1126 is a selective and orally active sphingosine-1-phosphate (S1P) agonist, with EC₅₀ values of 7.12 nM, 517 nM for hS1P₁ and hS1P₃, respectively. ASP1126 decreases the number of peripheral lymphocytes, naive T cells, central memory T cells and effector memory T cells in the peripheral blood. ASP1126 has the potential to be applied in clinical transplantation with improved 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.

(S)-PF-462991 is a direct-acting S1P_1,5 agonist.

Ginkgolic acid 2-phosphate is a potent sphingosine 1-phosphate agonist. Ginkgolic acid 2-phosphate induces ERK phosphorylation. Ginkgolic acid 2-phosphate interactes with S1P1.

Siponimod-d₁₁ (BAF-312-d₁₁) is deuterium labeled Siponimod (HY-12355). Siponimod 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.

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.

S1P1 agonist 5 is a selective and orally active S1P1 agonist. S1P1 agonist 5 inhibits the lymphocyte egress from the lymphoid tissue to the peripheral blood. S1P1 agonist 5 has the potential for the research of multiple sclerosis (MS).

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.

GSK2018682 hydrochloride is an agonist for S1P1 and S1P5 receptor with pEC₅₀s of 7.7 and 7.2, respectively, and has no agonist activity towards human S1P2, S1P3, or S1P4. GSK2018682 hydrochloride is used in the research of multiple sclerosis.

RP-001 is a picomolar short-acting S1P1 (EDG1) selective agonist, with an EC₅₀ of 9 pM. RP-00 induces internalization and polyubiquitination of S1P1. RP-001 has little activity on S1P2-S1P4 and only moderate affinity for S1P5.

GSK2263167 is a S1P1 receptor agonist

CS-0777-P, the phosphorylated form of CS-0777, acts as a potent and selective modulator of the S1P receptor-1 (S1P1). It exhibits approximately 320-fold higher agonist activity for human S1P1 compared to S1P3, with an EC50 of 1.1 nM. In pharmacological studies, CS-0777-P demonstrated significant effects in vitro as an S1P1 and S1P3 agonist, leading to lowered peripheral blood lymphocyte counts and suppressive effects on experimental autoimmune encephalomyelitis (EAE) in rats. Pharmacokinetic studies in rats revealed rapid lymphocyte count reductions following oral administration, making CS-0777 a promising candidate currently undergoing clinical trials for the treatment of multiple sclerosis (MS).

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.

CYM5181 is a novel S1P1 agonist with a pEC₅₀ value of -8.47.