| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
YM-244769 targets the Na+/Ca2+ exchanger (NCX), a membrane transport protein that exchanges sodium and calcium ions across the plasma membrane. The compound preferentially inhibits the NCX3 isoform. NCX plays a critical role in maintaining intracellular calcium homeostasis, particularly in excitable tissues such as the heart, brain, and kidney. By inhibiting NCX-mediated Ca2+ entry, YM-244769 protects against calcium overload-induced cell damage. The compound has IC50 values of 18 nM for NCX3 and 50 nM for NCX unidirectional outward current (Ca2+ entry mode).
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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 inhibits NCX3 with an IC50 of 18 nM and NCX unidirectional outward current (Ca2+ entry mode) with an IC50 of 50 nM. The compound shows potent protective effects on neurons and kidneys. It has been used in cellular assays to study the role of NCX in calcium homeostasis and cell survival. However, detailed in vitro activity data against other targets are not extensively reported. |
| 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].
In vivo, YM-244769 has been studied for its protective effects on neurons and kidneys. As an orally active NCX inhibitor, it has potential applications in conditions involving calcium overload, such as ischemia-reperfusion injury, neurodegenerative diseases, and renal injury. The compound shows oral bioavailability and has been used in preclinical studies. However, specific in vivo efficacy data and dosing regimens are not extensively detailed. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for YM-244769 typically involve NCX activity assays using cells expressing NCX isoforms. Cells are loaded with a calcium-sensitive dye (e.g., Fura-2 or Fluo-4) and perfused with solutions containing varying sodium and calcium concentrations. NCX-mediated calcium flux is measured by fluorescence microscopy or plate reader. The compound (0.001-100 μM) is applied, and inhibition of NCX-mediated calcium entry is measured. IC50 values are determined from dose-response curves.
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| 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. In vitro cellular assays for YM-244769 use neuronal cell lines (e.g., SH-SY5Y, primary cortical neurons) or renal cell lines. Cells are cultured in appropriate media and treated with various concentrations of the compound (0.001-10 μM) for 1-24 hours. Calcium overload is induced by high potassium or ouabain treatment. Cell viability is assessed using MTT or LDH release assays. Intracellular calcium levels are measured using fluorescent calcium indicators. NCX activity is assessed by measuring sodium-dependent calcium influx. |
| 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 studies with YM-244769 would typically use rodent models of ischemia-reperfusion injury, stroke, or renal injury. The compound is administered orally or intraperitoneally at doses of 1-30 mg/kg. In stroke models, infarct volume and neurological deficits are assessed. In renal injury models, kidney function (serum creatinine, BUN) and histopathology are evaluated. Neuroprotection is assessed by neuronal survival and behavioral outcomes. However, specific protocols are not extensively detailed. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of YM-244769: The compound is orally active, indicating good oral bioavailability. It has a molecular weight of 443.47. Specific PK parameters such as Cmax, Tmax, AUC, half-life, and tissue distribution are not extensively reported. The compound is expected to be metabolized by hepatic CYP450 enzymes and distributed to tissues expressing NCX, including the brain and kidneys.
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| Toxicity/Toxicokinetics |
The toxicity profile of YM-244769 is not extensively reported. As an NCX inhibitor, potential toxicities may include effects on cardiac function, as NCX plays a critical role in cardiac calcium handling. The compound is for research use only and not for human therapeutic use. Standard toxicity studies would include cardiovascular safety assessment (hERG, blood pressure, heart rate) and acute toxicity in rodents.
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| References |
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| Additional Infomation |
YM-244769 (CAS 838819-70-8) is a potent, selective, orally active Na+/Ca2+ exchanger (NCX) inhibitor that preferentially inhibits NCX3 with IC50 values of 18 nM and 50 nM. It has a molecular formula of C26H22FN3O3 and a molecular weight of 443.47. The compound shows potent protective effects on neurons and kidneys and has potential applications in ischemia-reperfusion injury and neurodegenerative disease research. It is available for research purposes only.
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| Molecular Formula |
C26H22FN3O3
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| Molecular Weight |
443.469589710236
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| Exact Mass |
443.164
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| CAS # |
838819-70-8
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| Related CAS # |
YM-244769 hydrochloride;837424-39-2;YM-244769 dihydrochloride;1780390-65-9
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| PubChem CID |
11442117
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
4.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
33
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| Complexity |
601
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1C=CC(OC2C=CC(OCC3C=C(F)C=CC=3)=CC=2)=NC=1)NCC1C=C(N)C=CC=1
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| InChi Key |
JZMLHJRKSJXARY-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
N-[(3-aminophenyl)methyl]-6-[4-[(3-fluorophenyl)methoxy]phenoxy]pyridine-3-carboxamide
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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 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)
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| Solubility (In Vitro) |
DMSO : ~120 mg/mL (~270.59 mM)
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| 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.
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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