Orally active, potent and selective sphingosine 1-phosphate (S1P) receptor 3 (S1P3; S1PR3) antagonist with in vitro and in vivo efficacy.
TY-52156 is a potent sphingosine 1-phosphate (S1P) receptor 3 (S1P3; S1PR3) antagonist that selectively inhibits S1P-stimulated Ca2+ response in human S1P3-expressing cells (Ki = 110 nM) and Eu-GTP binding to S1P3-containing membranes over those of S1P1/2/4/5. TY-52156 inhibits S1P3-dependent signaling events in human coronary artery smooth muscle cells (1 μM), S1P3-dependent coronary flow decrease in perfused rat hearts, as well as S1P3-mediated acute mechanical pain in mice (10 nmol/20 μL/paw id.) and bradycardia in anesthetized rats (30 mg/kg TY-52156 p.o.) in vivo with good oral bioavailability (F = 70.9%; 1 mg/kg p.o. in rats).
Sphingosine 1-phosphate (S1P) induces diverse biological responses in various tissues by activating specific G protein-coupled receptors (S1P(1)-S1P(5) receptors). The biological signaling regulated by S1P(3) receptor has not been fully elucidated because of the lack of an S1P(3) receptor-specific antagonist or
Medical science monitor : international medical journal of experimental and clinical research, 24, 1912-1923 (2018-04-02)
BACKGROUND Triple negative breast cancer (TNBC) has a more aggressive recurrence. Previous reports have demonstrated that sphingosine kinase 1 (SphK1) is a crucial regulator of breast cancer progression. However, the correlation of SphK1 with clinical prognosis has been poorly investigated.
Biochimica et biophysica acta, 1861(11), 1840-1851 (2016-09-13)
Breast cancer is one of the most common and devastating malignancies among women worldwide. Recent evidence suggests that malignant progression is also driven by processes involving the sphingolipid molecule sphingosine 1-phosphate (S1P) and its binding to cognate receptor subtypes on
Experimental and therapeutic medicine, 15(6), 5007-5016 (2018-05-29)
Thyroid carcinoma is characterized by an aggressive behavior, lack of effective targeted therapies and a high rate of relapse. Sphingosine kinase 1 (SPHK1) has been reported to be a critical regulatory factor in the progression of thyroid carcinoma, but the
Pharmacology research & perspectives, 5(6) (2017-12-12)
Sphingosine-1-phosphate receptor 1 (S1P1 ) modulators sequester circulating lymphocytes within lymph nodes, thereby preventing potentially pathogenic autoimmune cells from exiting into the blood stream and reaching inflamed tissues. S1P1 receptor modulation may thus offer potential to treat various autoimmune diseases.
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