[CAS NO. 1780390-65-9] YM-244769dihydrochloride
PRODUCTS SPECIFICATIONS [1780390-65-9]
DESCRIPTION [1780390-65-9]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 516.39 |
| Molecular Formula | C26H24Cl2FN3O3 |
| SMILES | O=C(C1=CC=C(OC2=CC=C(OCC3=CC=CC(F)=C3)C=C2)N=C1)NCC4=CC=CC(N)=C4.Cl.Cl |
Summary
YM-244769 dihydrochloride is a potent, selective and orally active Na + /Ca 2+ exchanger ( NCX ) inhibitor. YM-244769 dihydrochloride preferentially inhibits NCX3 and suppresses the unidirectional outward NCX current (Ca 2+ entry mode), with IC 50 s 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] .
IC50 & Target
IC 50 : 18 nM (NCX3), 68 nM (NCX1), 96 nM (NCX2) [1]
In Vitro
YM-244769 (0.003-1 μM) inhibits dose dependently the initial rates of
45
Ca
2+
uptake into NCX1, NCX2, and NCX3 transfectants with IC
50
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-PK
1
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 IC
50
against the unidirectional outward I
NCX
(Ca
2+
entry mode) is 0.05 μM. The IC
50
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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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. |
In Vivo
YM-244769 (0.1-1 mg/kg; p.o.; once) exhibits dose-dependently natriuretic action in mice and significantly increases urinary excretion of Ca 2+ as well as Ca 2+ /Cr ratio [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Wild-type C57BL/6J mice and NCX-KO mice [2] |
| Dosage: | 0.1, 0.3 and 1 mg/kg |
| Administration: | Oral administration, once |
| Result: | Caused a dose-dependent increase (up to approximately 200%) in urine volume and urinary excretion of electrolytes (Na + , K + and Cl - ). Natriuretic actions were equivalently observed in NCX1-KO and WT, but disappeared in NCX2-KO and double KO. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : 100 mg/mL ( 193.65 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.9365 mL | 9.6826 mL | 19.3652 mL |
| 5 mM | 0.3873 mL | 1.9365 mL | 3.8730 mL |
| 10 mM | 0.1937 mL | 0.9683 mL | 1.9365 mL |
References
- [1] Takahiro Iwamoto , et al. YM-244769, a Novel Na /Ca Exchange Inhibitor That Preferentially Inhibits NCX3, Efficiently Protects Against hypoxia/reoxygenation-induced SH-SY5Y Neuronal Cell Damage. Mol Pharmacol. 2006 Dec;70(6):2075-
- [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.