PSB 0739

PSB-0739 is a high-affinity potent, competitive, nonselective platelet P2Y12 receptor antagonist with a Ki values of 24.9 nM. The P2Y12 receptor plays a crucial role in platelet aggregation. Antithrombotic effect[1].

Research Areas >> Cardiovascular Disease

Signaling Pathways >> GPCR/G Protein >> P2Y Receptor

PSB-0739 is a potent competitive non-nucleotide antagonist at the human P2Y12 receptor with a pA2 value of 9.8[2]. PSB-0739 inhibits ADP-evoked Ca2+ responses with an EC50 of 5.4±1.8 μM and causes a rightward parallel shift in the ADP concentration–response curve in THP-1 cells[3]. Cell Viability Assay[3] Cell Line: THP-1 monocytic cell line Concentration: 10 nM, 100 nM, 1 μM, 10 μM Incubation Time: Result: Attenuated ADP-evoked responses (IC50=5.4±1.8 μM).

PSB-0739 (0.01-0.3 mg/kg, intrathecally) has dose-dependent and significant antihyperalgesic effect in low doses. The minimal effective dose (mED) is 0.1 mg/kg[4]. Animal Model: Male Wistar rats, 150-250 g, 6-8/group[4] Dosage: 0.01, 0.03, 0.1, 0.3 mg/kg Administration: Intrathecal injection ( i.t.) Result: Displayed a dose-dependent inhibitory effect on mechanical hyperalgesia in the range of 0.01–0.1 mg/kg.

[1]. Younis Baqi, et al. High-affinity, non-nucleotide-derived competitive antagonists of platelet P2Y₁₂ receptors. J Med Chem. 2009 Jun 25;52(12):3784-93.

[2]. Kristina Hoffmann, et al. Interaction of new, very potent non-nucleotide antagonists with Arg256 of the human platelet P2Y₁₂ receptor. J Pharmacol Exp Ther. 2009 Nov;331(2):648-55.

[3]. J J Micklewright,et al. P2Y 12 receptor modulation of ADP-evoked intracellular Ca²⁺ signalling in THP-1 human monocytic cells. Br J Pharmacol.2018 Jun;175(12):2483-2491.

[4]. Gergely Horváth, et al. Central P2Y₁₂ receptor blockade alleviates inflammatory and neuropathic pain and cytokine production in rodents. Neurobiol Dis. 2014 Oct;70(100):162-78.