YM-244769 dihydrochloride is a potent, selective and orally active Na+/Ca2+ exchanger (NCX) inhibitor. YM-244769 dihydrochloride preferentially inhibits NCX3 and suppresses the unidirectional outward NCX current (Ca2+ entry mode), with IC50s of 18 nM and 50 nM, respectively. YM-244769 dihydrochloride efficiently protects against hypoxia/reoxygenation-induced SH-SY5Y neuronal cell damage. YM-244769 dihydrochloride can also increase urine volume and urinary excretion of electrolytes in mice[1][2][3].
YM-244769 (0.003-1 μM) inhibits dose dependently the initial rates of 45Ca2+ uptake into NCX1, NCX2, and NCX3 transfectants with IC50 values of 68 ± 2.9, 96 ± 3.5, and 18 ± 1.0 nM, respectively[1].YM-244769 (0.3 or 1 μM) efficiently protects against the hypoxia/reoxygenation-induced lactate dehydrogenase (LDH) release in SH-SY5Y cells and in LLC-PK1 cells (1 μM)[1].YM-244769 possesses reverse mode-selectivity[1].YM-244769 (1 and 10 μM) inhibits NCX current (INCX) in a concentration- and [Na+]i-dependent manner, the IC50 against the unidirectional outward INCX (Ca2+ entry mode) is 0.05 μM. The IC50 values against the bidirectional outward and inward INCX are similar and approximately 100 nM with a Hill coefficient of about 1[3].YM-244769 is trypsin-insensitive[3].
YM-244769 (0.1-1 mg/kg; p.o.; once) exhibits dose-dependently natriuretic action in mice and significantly increases urinary excretion of Ca2+ as well as Ca2+/Cr ratio[2].
[1]. Takahiro Iwamoto , et al. YM-244769, a Novel Na+/Ca2+ Exchange Inhibitor That Preferentially Inhibits NCX3, Efficiently Protects Against hypoxia/reoxygenation-induced SH-SY5Y Neuronal Cell Damage. Mol Pharmacol. 2006 Dec;70(6):2075-83.
[2]. Gotoh Y, et al. Genetic knockout and pharmacologic inhibition of NCX2 cause natriuresis and hypercalciuria. Biochem Biophys Res Commun. 2015 Jan 9;456(2):670-5.
[3]. Yamashita K, et al. Inhibitory effect of YM-244769, a novel Na+/Ca2+ exchanger inhibitor on Na+/Ca2+ exchange current in guinea pig cardiac ventricular myocytes. Naunyn Schmiedebergs Arch Pharmacol. 2016 Nov;389(11):1205-1214.