YM-244769 is a potent, selective, orally bioactive Na+/Ca2+ exchanger (NCX) inhibitor. YM-244769 preferentially inhibits NCX3 and inhibits NCX unidirectional outward current (Ca2+ entry mode), with IC50s of 18 nM and 50 nM respectively. YM-244769 can effectively prevent hypoxia/reoxygenation-induced SH-SY5Y neuronal cell damage. YM-244769 also increased urine output and urinary electrolyte excretion in mice.

Physicochemical Properties

Molecular Formula	C26H22FN3O3
Molecular Weight	443.469589710236
Exact Mass	443.164
CAS #	838819-70-8
Related CAS #	YM-244769 hydrochloride;837424-39-2;YM-244769 dihydrochloride;1780390-65-9
PubChem CID	11442117
Appearance	Off-white to light yellow solid powder
LogP	4.4
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	8
Heavy Atom Count	33
Complexity	601
Defined Atom Stereocenter Count	0
SMILES	O=C(C1C=CC(OC2C=CC(OCC3C=C(F)C=CC=3)=CC=2)=NC=1)NCC1C=C(N)C=CC=1
InChi Key	JZMLHJRKSJXARY-UHFFFAOYSA-N
InChi Code	InChI=1S/C26H22FN3O3/c27-21-5-1-4-19(13-21)17-32-23-8-10-24(11-9-23)33-25-12-7-20(16-29-25)26(31)30-15-18-3-2-6-22(28)14-18/h1-14,16H,15,17,28H2,(H,30,31)
Chemical Name	N-[(3-aminophenyl)methyl]-6-[4-[(3-fluorophenyl)methoxy]phenoxy]pyridine-3-carboxamide
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	At IC50 values of 68 ± 2.9, 96 ± 3.5, and 18 ± 1.0 nM, respectively, YM-244769 (0.003-1 μM) dose-dependently reduces the initial rate of 45Ca2+ absorption by NCX1, NCX2, and NCX3 transfectants [1]. Lactate dehydrogenase (LDH) release in SH-SY5Y cells and LLC-PK1 cells is efficiently inhibited by YM-244769 (0.3 or 1 μM) [1]. Reverse mode selectivity is possessed by YM-244769 [1]. At an IC50 of 0.05 μM, YM-244769 (1 and 10 μM) inhibits unidirectional outward INCX (Ca2+ entry mode) in a concentration- and [Na+]i-dependent manner. With a Hill coefficient of about 1, the IC50 values for bidirectional outward and inward INCX are comparable at about 100 nM [3]. Trypsin sensitivity is absent in YM-244769 [3].
ln Vivo	In mice, YM-244769 (0.1–1 mg/kg; oral; once) dramatically raises the Ca2+/Cr ratio and urine Ca2+ excretion in a dose-dependent manner [2].
Cell Assay	Cell Viability Assay[1] Cell Types: SH-SY5Y cells treated with NCX1 or NCX3 antisense nucleic acid Tested Concentrations: 0.3 and 1 μM Incubation Duration: Experimental Results: Hypoxia/reoxygenation-induced LDH release was Dramatically attenuated: cells in treated cells The reduction in damage was greater in cells treated with NCX3 antisense (61% increase) than in cells treated with NCX1 antisense (35% reduction). In SH-SY5Y cells treated with NCX1 antisense, 0.3 or 1 μM inhibited hypoxia/reoxygenation-induced cell damage more effectively than cells treated with NCX3 antisense.
Animal Protocol	Animal/Disease Models: wild-type C57BL/6J mice and NCX-KO mice [2] Doses: 0.1, 0.3 and 1 mg/kg Route of Administration: Oral administration once Experimental Results:Caused a dose-dependent increase (up to approximately 200%) in urine output and urinary electrolyte excretion (Na+, K+, and Cl-). The same natriuretic effect was observed in NCX1-KO and WT but disappeared in NCX2-KO and double KO.
References	[1]. Iwamoto T, Kita S. 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]. Genetic knockout and pharmacologic inhibition of NCX2 cause natriuresis and hypercalciuria. Biochem Biophys Res Commun. 2015 Jan 9;456(2):670-5. [3]. 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.

Solubility Data

Solubility (In Vitro)

DMSO : ~120 mg/mL (~270.59 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.69 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2549 mL	11.2747 mL	22.5494 mL
	5 mM	0.4510 mL	2.2549 mL	4.5099 mL
	10 mM	0.2255 mL	1.1275 mL	2.2549 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.