YM-244769 (hydrochloride)

YM-244769 hydrochloride is a potent, selective and orally active Na⁺/Ca²⁺ exchanger (NCX) inhibitor. YM-244769 hydrochloride preferentially inhibits NCX3 and suppresses the unidirectional outward NCX current (Ca²⁺ entry mode), with IC₅₀s of 18 nM and 50 nM, respectively. YM-244769 hydrochloride efficiently protects against hypoxia/reoxygenation-induced SH-SY5Y neuronal cell damage. YM-244769 hydrochloride can also increase urine volume and urinary excretion of electrolytes in mice^[1][2][3]. IC50 & Target: IC₅₀: 18 nM (NCX3)^[1] In Vitro: 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 (I_NCX) in a concentration- and [Na⁺]_i-dependent manner, the IC₅₀ against the unidirectional outward I_NCX (Ca²⁺ entry mode) is 0.05 μM. The IC₅₀ values against the bidirectional outward and inward I_NCX are similar and approximately 100 nM with a Hill coefficient of about 1^[3].
YM-244769 is trypsin-insensitive^[3].
In Vivo: YM-244769 (0.1-1 mg/kg; p.o.; once) exhibits dose-dependently natriuretic action in mice and significantly increased urinary excretion of Ca²⁺ as well as Ca²⁺/Cr ratio^[2].