YM-244769 HCl is a potent, selective, orally bioactive Na+/Ca2+ exchanger (NCX) inhibitor. YM-244769 HCl preferentially inhibits NCX3 and inhibits NCX unidirectional outward current (Ca2+ entry mode), with IC50 of 18 nM and 50 nM respectively. YM-244769 HCl can effectively prevent hypoxia/reoxygenation-induced SH-SY5Y neuronal cell damage. YM-244769 HCl also increases urine output and urinary electrolyte excretion in mice.

Physicochemical Properties

Molecular Formula	C26H22N3O3F.2[HCL]
Molecular Weight	516.39146
Exact Mass	515.118
CAS #	837424-39-2
Related CAS #	YM-244769 dihydrochloride;1780390-65-9;YM-244769;838819-70-8
PubChem CID	90488952
Appearance	Off-white to light yellow solid powder
LogP	7.864
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	8
Heavy Atom Count	35
Complexity	601
Defined Atom Stereocenter Count	0
InChi Key	OCKIUNLKEPKCRE-UHFFFAOYSA-N
InChi Code	InChI=1S/C26H22FN3O3.2ClH/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);2*1H
Chemical Name	N-[(3-aminophenyl)methyl]-6-[4-[(3-fluorophenyl)methoxy]phenoxy]pyridine-3-carboxamide;dihydrochloride
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
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 urinary Ca2+ excretion in a dose-dependent manner [2].
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 : ~100 mg/mL (~208.36 mM)

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		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

*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.