YM-244769 dihydrochloride manufacturers
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| | YM-244769 dihydrochloride Basic information |
| Product Name: | YM-244769 dihydrochloride | | Synonyms: | YM-244769 dihydrochloride;YM244769.HCl;N-(3-Aminobenzyl)-6-(4-((3-fluorobenzyl)oxy)phenoxy)nicotinamide dihydrochloride;3-Pyridinecarboxamide, N-[(3-aminophenyl)methyl]-6-[4-[(3-fluorophenyl)methoxy]phenoxy]-, hydrochloride (1:2);N-(3-aminobenzyl)-6-(4-((3-fluorobenzyl)oxy)phenoxy)nicotinamide， hydrochloride (1:2) | | CAS: | 1780390-65-9 | | MF: | C26H24Cl2FN3O3 | | MW: | 0 | | EINECS: | | | Product Categories: | | | Mol File: | Mol File | ![YM-244769 dihydrochloride Structure]() |
| | YM-244769 dihydrochloride Chemical Properties |
| storage temp. | 4°C, away from moisture | | solubility | DMSO : 100 mg/mL (193.65 mM; Need ultrasonic) | | form | Solid | | color | Off-white to pink | | 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) | | InChIKey | JZMLHJRKSJXARY-UHFFFAOYSA-N | | SMILES | O=C(C1=CC=C(OC2=CC=C(OCC3=CC=CC(F)=C3)C=C2)N=C1)NCC4=CC=CC(N)=C4 |
| WGK Germany | WGK 3 | | Storage Class | 11 - Combustible Solids |
| | YM-244769 dihydrochloride Usage And Synthesis |
| Uses | YM 244769, is Na+/Ca2+ exchange inhibitor (reverse mode). It can also act as a neuroprotective, that protects against hypoxia/reoxygenation-induced cell damage in neuronal SH-SY5Y cells expressing NCX1 and NCX3. | | Biological Activity | YM-244769 dihydrochloride is a potent, selective and orally active Na+/Ca2+ exchanger (NCX) inhibitor. YM-244769 dihydrochloride preferentially inhibits NCX3 and suppresses the unidirectional outward NCX current (Ca2+ entry mode), with IC50s 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].
YM-244769 (0.003-1 μM) inhibits dose dependently the initial rates of 45Ca2+ uptake into NCX1, NCX2, and NCX3 transfectants with IC50 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-PK1 cells (1 μM)[1].YM-244769 possesses reverse mode-selectivity[1].YM-244769 (1 and 10 μM) inhibits NCX current (INCX) in a concentration- and [Na+]i-dependent manner, the IC50 against the unidirectional outward INCX (Ca2+ entry mode) is 0.05 μM. The IC50 values against the bidirectional outward and inward INCX are similar and approximately 100 nM with a Hill coefficient of about 1[3].YM-244769 is trypsin-insensitive[3].
YM-244769 (0.1-1 mg/kg; p.o.; once) exhibits dose-dependently natriuretic action in mice and significantly increases urinary excretion of Ca2+ as well as Ca2+/Cr ratio[2]. | | 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 Ca2+ as well as Ca2+/Cr ratio[2]. | 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. |
| | storage | Desiccate at RT | | References | [1]. Takahiro Iwamoto , et al. 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]. 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. |
| | YM-244769 dihydrochloride Preparation Products And Raw materials |
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