1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemELomerizine dihydrochlorideCat. No.: HY-B0768ACAS No.: 101477-54-7Synonyms: KB-2796分式: CHClFNO分量: 541.46作靶點: Calcium Channel作通路: Membrane Transporter/Ion Channel; Neuronal Signaling儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80

2、C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 100 mg/mL (184.69 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.8469 mL 9.2343 mL 18.4686 mL5 mM 0.3694 mL 1.8469 mL 3.6937 mL10 mM 0.1847 mL 0.9234 mL 1.8469 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Lomeri

3、zine dihydrochloride種雙重 的 L- 和 T 型電壓門控鈣通道 (calcium channel) 拮抗劑。IC50 & Target T-type calcium channel L-type calcium channel體外研究Lomerizine is an antagonist of L- and T-type voltagegated calcium channels and transient receptor potentialchannel 5 transient receptor potential channels. Lomerizine is a d

4、ual L/T-type channel blocker used for1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEprophylaxis of migraine. To demonstrate the effectiveness of Lomerizine in limiting intracellular Ca2+, itsability to inhibit glutamate-induced death of motor neurons and the associated rise in cytosolic Ca2+ iseva

5、luated. Lomerizine inhibits the low- and high-voltage activated Ca2+ currents in dissociated rat brainneurons at a threshold concentration of 0.01 M and IC50 of 1.9 M and H2O2-induced Ca2+ influx inhippocampal neurons is inhibited by 1 M Lomerizine. Pre-treatment with 1 M Lomerizine significantlyred

6、uces acute death of motor neurons in spinal cord-DRG cultures exposed to 50 M glutamate, aconcentration that kills approximately 40% of motor neurons in the culture by 6 h, and inhibits the rise incytosolic Ca2+ that occurs with glutamate treatment. 0.5 M Lomerizine is sufficient to significantly pr

7、eventthe mitochondrial fragmentation of mitochondria induced by SOD1G93A 1. Lomerizine increases thecytotoxicity of Adriamycin (ADM) and the apoptosis induced by ADM or Vincristine (VCR) in K562/ADM cells.At the concentration of 3, 10 and 30M, Lomerizine reduces the IC50 value of ADM from 79.03 M to

8、 28.14,8.16 and 3.16 M, respectively. Lomerizine increases the intracellular accumulation of ADM and inhibits theefflux of Rh123 in K562/ ADM cells. No change in P-gp expression is observed after the treatment ofLomerizine for 72 h. Lomerizine has strong reversal effect on MDR in K562/ADM cells by i

9、nhibiting P-gpfunction 2.體內(nèi)研究 To determine whether Ca2+ signaling molecules mediate NMDA-induced neurotoxicity in p50-deficient mice,the neuroprotective effects of chemical reagents are examined, which act on the Ca2+-signaling pathwayincluding CaN activation, on NMDA-induced RGC death. The p50-defi

10、cient mice at 2 months of age, showingnormal RGC survival, undergo intraperitoneal pretreatments with a NMDA antagonist, MK801 or Memantine;calcium blocker, Lomerizine; and CaN inhibitor, Tacrolimus, daily for 1 week before the injection of 5 nMNMDA. The chronic administration of Lomerizine or Tacro

11、limus to KO mice for 6 months results in anincrease in surviving RGC numbers (p 3. Lomerizine (KB-2796; 0.3 and 1 mg/kg, i.v.) dose-dependentlyincreases cerebral blood flow significantly at 30 min and 15 min, respectively, after its administration.Lomerizine (1 mg/kg, i.v.) significantly attenuates

12、the expression of c-Fos-like immunoreactivity in theipsilateral frontoparietal cortex 4.PROTOCOLCell Assay 2 MTT assay is used to determine the influence of Lomerizine on the cytotoxicity of Adriamycin (ADM). Theeffect of Lomerizine (3, 10 and 30 M) on the apoptosis induced by ADM and Vincristine (V

13、CR) in K562/ADMcells is detected using flow cytometry. Intracellular accumulation of ADM is measured by fluorescencespectrophotometry. Flow cytometry is used to investigate the efflux of Rhodamine 123 (Rh123) and theexpression of P-glycoprotein (P-gp) in K562/ADM cells 2.MCE has not independently co

14、nfirmed the accuracy of these methods. They are for reference only.Animal Mice 3Administration 34 The p50-deficient mice and wild-type mice aged 2 months are daily pre-treated intraperitoneally withMemantine (10 mg/kg), MK-801 (0.5 mg/kg), Lomerizine (1 mg/kg), or Tacrolimus (2, 0.5 and 0.2 mg/kg) f

15、orone week before the NMDA injection. These mice are given an intravitreous injection of 5 nM NMDA, whichis a relatively low concentration for causing neurotoxicity 3.Rats 4Male Wistar rats weighing 250 to 350 g are housed in an air-conditioned room at 250C with 555%2/3 Master of Small Molecules 您邊的

16、抑制劑師www.MedChemEhumidity and given food and water ad libitum. Lomerizine is injected i.v. in a volume of 1 mL/kg body weight.Effects of Lomerizine (0.3 mg/kg, i.v., or 1 mg/kg, i.v.) are measured on cerebral cortical blood flow measuredby laser Doppler flowmetry (CBFLDF) in anaesthetized rats 4.MCE

17、has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Tran LT, et al. The voltage-gated calcium channel blocker Lomerizine is neuroprotective in motor neurons expressing mutant SOD1, butnot TDP-43. J Neurochem. 2014 Aug;130(3):455-66.2. Zhu HJ, et al

18、. Reversal of multidrug resistance by Lomerizine in K562/ADM cells. Yao Xue Xue Bao. 2004 May;39(5):333-7.3. Nakamura-Yanagidaira T, et al. Development of spontaneous neuropathy in NF-Bp50-deficient mice by calcineurin-signal involvingimpaired NF-B activation. Mol Vis. 2011;17:2157-70.4. Shimazawa M, et al. Effects of Ca2+ channel blockers on cortical hypoperfusion and expression of c-Fos-like immunoreactivity afterc