MRS4917 is a potent and selective orally active P2Y14 receptor (hP2Y14R) antagonist, with an IC50 of 2.88 nM and a Ki of 1.67 nM, demonstrating over 18,000-fold selectivity against P2Y6R (IC50= 54 μM). It effectively reverses established mechanical allodynia in a chronic sciatic nerve compression (CCI) mouse model without affecting thermoregulation when administered orally. MRS4917 is applicable for research in neurological disorders.

P2Y14 receptor (human):2.88 nM

MRS4917 (compound 11) (0.1-10 μM, 72 hours) demonstrates excellent safety in vitro, with low cytotoxicity, no significant inhibition of CYP450 enzymes (CYP2D6 and CYP3A4), and high selectivity in broad off-target screening (only weakly affecting the α2C receptor).

MRS4917, when administered either as a single oral dose of 1.37 mg/kg or via intraperitoneal injection at 4.58 mg/kg, alleviates mechanical allodynia in a chronic sciatic nerve compression (CCI) mouse model. In wild-type C57BL/6J mice, a single intraperitoneal injection of MRS4917 at 10 mg/kg shows no effect on body temperature or spontaneous activity. Additionally, an intraperitoneal injection of 10 mg/kg MRS4917, given 60 minutes before MRS2905, effectively blocks the hypothermic effect induced by the P2Y14 receptor agonist MRS2905 (5 mg/kg, intraperitoneal) in male C57BL/6J mice.