| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
YM-244769 HCl targets the Na⁺/Ca²⁺ exchanger (NCX), a membrane transporter that plays a critical role in maintaining intracellular calcium homeostasis. NCX mediates the exchange of Na⁺ and Ca²⁺ across the plasma membrane, with the direction of transport depending on the electrochemical gradients. The compound preferentially inhibits the NCX3 isoform and inhibits the NCX unidirectional outward current (Ca²⁺ entry mode), with IC50 values of 18 nM and 50 nM, respectively. This inhibition can protect cells from calcium overload during hypoxia/reoxygenation injury.
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| 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].
In vitro, YM-244769 HCl dose-dependently reduces the initial rate of ⁴⁵Ca²⁺ absorption by NCX1, NCX2, and NCX3 transfectants with IC50 values of 68 ± 2.9, 96 ± 3.5, and 18 ± 1.0 nM, respectively. It efficiently inhibits lactate dehydrogenase (LDH) release in SH-SY5Y cells and LLC-PK1 cells at 0.3 or 1 μM. The compound possesses reverse mode selectivity. At an IC50 of 0.05 μM, it inhibits unidirectional outward INCX (Ca²⁺ entry mode) in a concentration- and [Na⁺]i-dependent manner. |
| 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].
In vivo, YM-244769 HCl (0.1–1 mg/kg; oral; once) dramatically raises the Ca²⁺/Cr ratio and urinary Ca²⁺ excretion in a dose-dependent manner in mice. It causes 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. These studies demonstrate its diuretic effects. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays are not applicable to YM-244769 HCl as it is a transporter inhibitor. The compound's activity is characterized in ion flux assays. Cells expressing NCX isoforms are loaded with ⁴⁵Ca²⁺, and the initial rate of Ca²⁺ uptake is measured in the presence of varying concentrations of the compound. IC50 values of 68, 96, and 18 nM for NCX1, NCX2, and NCX3, respectively, are determined.
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| Cell Assay |
Cell-based assays for YM-244769 HCl are conducted in SH-SY5Y neuronal cells and LLC-PK1 cells. Cells are subjected to hypoxia/reoxygenation injury in the presence of the compound at 0.3 or 1 μM. Cell damage is assessed by measuring LDH release. These assays demonstrate the compound's neuroprotective effects.
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| 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. In vivo animal experiments with YM-244769 HCl are conducted in wild-type C57BL/6J mice and NCX-KO mice. The compound is administered orally at doses of 0.1, 0.3, and 1 mg/kg. Urine output and urinary electrolyte excretion (Na⁺, K⁺, Cl⁻, Ca²⁺) are measured. These studies characterize the compound's diuretic effects and its isoform selectivity. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of YM-244769 HCl include oral bioavailability. The compound has a molecular formula of C26H22N3O3F·2HCl and a molecular weight of 516.39. Appearance: Off-white to light yellow solid powder. LogP: 7.864. Storage: powder at -20°C for 3 years; in solvent at -80°C for 6 months. Specific data on half-life, Cmax, and AUC are not available.
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| Toxicity/Toxicokinetics |
Safety and toxicology data for YM-244769 HCl are limited. The compound is for research use only and is not approved for human therapeutic use. Standard laboratory safety precautions should be followed when handling the compound. No specific toxicity data are available.
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| References |
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| Additional Infomation |
YM-244769 HCl has CAS number 837424-39-2, molecular formula C26H22N3O3F·2HCl, and molecular weight 516.39. It is a potent, selective, and orally bioactive NCX inhibitor that preferentially inhibits NCX3 with IC50 = 18 nM. It protects against hypoxia/reoxygenation-induced neuronal damage and has diuretic effects. Purity: ≥98%. Not for human use; for research purposes only.
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| Molecular Formula |
C26H22N3O3F.2[HCL]
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| Molecular Weight |
516.39146
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| Exact Mass |
515.118
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| CAS # |
837424-39-2
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| Related CAS # |
YM-244769 dihydrochloride;1780390-65-9;YM-244769;838819-70-8
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| PubChem CID |
90488952
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
7.864
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
35
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| Complexity |
601
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
OCKIUNLKEPKCRE-UHFFFAOYSA-N
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| 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
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| Chemical Name |
N-[(3-aminophenyl)methyl]-6-[4-[(3-fluorophenyl)methoxy]phenoxy]pyridine-3-carboxamide;dihydrochloride
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~208.36 mM)
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| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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