2. Signaling Pathways
  3. GPCR/G Protein
  4. LPL Receptor
  5. S1PR3 Isoform

S1PR3

Sphingosine-1-phosphate receptor 3 (S1PR3) is a G protein-coupled receptor that regulates vascular tone and endothelial function[1]. Mechanistically, S1PR3 activation stimulates intracellular PI3K/Akt and ERK1/2 signaling, promoting extracellular matrix synthesis and vascular remodeling independent of Smad pathways[1]. In physiological models, S1PR3 contributes to blood pressure homeostasis and flow-mediated mechanotransduction, complementing S1PR1-mediated nitric oxide signaling[2][1]. Compared with S1PR1 and S1PR2, S1PR3 exhibits distinct pro-fibrotic potential and unique signaling bias, influencing fibroblast and endothelial responses differently[1][3]. In disease models, S1PR3 involvement has been implicated in pulmonary fibrosis and inflammatory vascular injury, where agonist-mediated activation enhances extracellular matrix deposition and endothelial remodeling[1]. Selective agonists and antagonists have been used to dissect S1PR3-specific effects, demonstrating that dual S1PR1/S1PR3 agonists amplify fibrotic signaling, whereas S1PR3-sparing modulators reduce off-target vascular responses[1][4]. For experimental applications, these pharmacological tools allow precise modulation of fibroblast differentiation, vascular remodeling, and inflammation, facilitating the development of targeted therapies without interfering with closely related isoforms[1][4][3]. Collectively, S1PR3 represents a functionally distinct S1P receptor with critical roles in cardiovascular physiology, fibrosis, and experimental modeling of vascular and pulmonary disease.

S1PR3 Related Products (10):

Cat. No. Product Name Effect Purity
  • HY-12355
    Siponimod
    		Agonist 99.95%
    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.
  • HY-10569
    Ponesimod
    		Agonist 99.78%
    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.
  • HY-119401
    CAY10444
    		Antagonist 98.0%
    CAY10444 (BML-241) is a sphingosine-1-phosphate 3 (S1P3) antagonist. CAY10444 inhibits by 37% S1P-induced increases in Ca2+ in HeLa cells expressing S1P3 receptors.
  • HY-111253
    CYM-5478
    		Agonist 99.90%
    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.
  • HY-176533
    S1PR5-IN-1
    		Inhibitor 99.58%
    S1PR5-IN-1 (Compound 7a) is a highly selective S1PR5 antagonist and orally bioavailable inhibitor with a human S1PR5 IC50 of 85.4 nM and human S1PR5 Kd of 2.173 nM.S1PR5-IN-1 binds to S1PR5 and inhibits natural killer cell migration toward sphingosine-1-phosphate.S1PR5-IN-1 can be used for the research of multiple sclerosis.
  • HY-14402
    AMG 369
    		Agonist
    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.
  • HY-NP203
    High density lipoprotein (human)
    		Activator 98.00%
    High density lipoprotein (human) (HDL (human)) is a human-derived high-density lipoprotein. High density lipoprotein can cross the blood-brain barrier, and partially acts on endothelial nitric oxide synthase (eNOS) by activating surface receptors such as SR-B1 and S1P3R, as well as intracellular signaling cascades involving Akt, PI3K and MAPK, thereby inducing the production of NO in endothelial cells. High density lipoprotein (human) can be used in research related to type 2 diabetes, Alzheimer's disease, cancer and atherosclerosis.
  • HY-12355A
    Siponimod hemifumarate
    		Agonist 99.64%
    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.
  • HY-113934
    L-threo Lysosphingomyelin (d18:1)
    		Agonist 98.0%
    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.
  • HY-108492
    TC-SP 14
    		Agonist
    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.