YM-244769 dihydrochloride

YM-244769 dihydrochloride is a potent Na+/Ca2+ exchange (NCX) inhibitor that preferentially inhibits NCX3 (IC50=18 nM). Neuronal and renal protection[1].

Research Areas >> Neurological Disease

YM-244769 preferentially inhibits intracellular Na+-dependent 45Ca2+ uptake via NCX3 (IC50=18 nM); the inhibition is 3.8- to 5.3-fold greater than for the uptake via NCX1 or NCX2, but it does not significantly affect extracellular Na+-dependent 45Ca2+ efflux via NCX isoforms[1]. 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, indicating that YM-244769 is approximately four to five times more selective to NCX3 than other isoforms[1]. YM-244769 (0.3 or 1 μM) efficiently suppresses the hypoxia/reoxygenation-induced cell damage in SH-SY5Y cells treated with NCX1 antisense (i.e., SH-SY5Y cells primarily expressing NCX3) more than in those treated with NCX3 antisense (i.e., SH-SY5Y cells primarily expressing NCX1)[1]. Cell Viability Assay[1] Cell Line: SH-SY5Y cells treated with NCX1 or NCX3 antisense Concentration: 0.3 and 1 μM Incubation Time: Result: Hypoxia/reoxygenation-induced LDH release was significantly attenuated: reduction in cell damage was greater in cells treated with NCX3 antisense (by 61%) than in cells treated with NCX1 antisense (by 35%). 0.3 or 1 μM efficiently suppressed the hypoxia/reoxygenation-induced cell damage in SH-SY5Y cells treated with NCX1 antisense more than in those treated with NCX3 antisense.

[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.