S1P3 Receptor Antagonist, TY-52156

A cell-permeable hydrazonamide derivative that acts as a selective and competitive antagonist of S1P3 receptor (K_i = 110 nM) and suppresses S1P-induced expansion of A549, LNCaP, U251MG, and OVCAR-5 cancer cells (~ 10 µM). Displays about 30-fold lower effect on S1P1, S1P2, S1P4, or S1P5 receptors and does not affect 24 different G-protein coupled receptors (~10 µM). Shown to block S1P-induced expression of Hes1 and reduce ALDH-positive cell population. Inhibits the tumorigenicity of SphK1-overexpressing ALDH-positive cells following chronic administration over a period of 6 weeks. Preferentially inhibits S1P-induced increase in [Ca2+]i and Rho activation in vascular smooth muscle cells. Shown to reduce S1P3 receptor-induced bradycardia in vivo in rats and diminishes coronary flow in perfused rat heart. Also shown to relax cerebral arteries precontracted with S1P.

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

A hydrazonamide derivative that suppresses the S1P-induced cancer stem cell expansion effects in multiple human cancer cell lines including, breast cancer MCF-7 cells, lung cancer A549 cells, glioma U251MG cells and ovarian cancer OVCAR-5 cells at 10 µM. Significantly inhibits the tumorigenicity of SphK1-overexpressing ALDH-positive cells after chronic continuous injection for 6 weeks (167mg/ml) in a mouse xenograft model. In addition, shown to suppress the S1P-induced effects such as Ca2+ increase and Rho activation in vascular smooth muscle cells and decrease of coronary flow in isolated perfused rat hearts.

Primary Target
S1P3

Packaged under inert gas

Toxicity: Standard Handling (A)

Following reconstitution, aliquot and freeze (-70°C). Stock solutions are stable for up to 4 weeks at -70°C.

Hirata, N., et al. 2014, Nat. Comm.5, in press.
Murakami, A., et al. 2010. Mol. Pharm.77, 704.

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