奎尼丁鹽酸鹽一水合物作用機(jī)制 - Medchemexpress - MCE中國(guó)

1、Product Data SheetQuinidine hydrochloride monohydrateCat. No.: HY-B1302CAS No.: 6151-40-2分式: CHClNO分量: 378.89作靶點(diǎn): Potassium Channel; Parasite作通路: Membrane Transporter/Ion Channel; Anti-infection儲(chǔ)存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 100 mg/mL (263.93 m

2、M; Need ultrasonic)H2O : 2.5 mg/mL (6.60 mM; Need ultrasonic)SolventMass1 mg 5 mg 10 mgConcentration制備儲(chǔ)備液1 mM 2.6393 mL 13.1964 mL 26.3929 mL5 mM 0.5279 mL 2.6393 mL 5.2786 mL10 mM 0.2639 mL 1.3196 mL 2.6393 mL請(qǐng)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(chǔ)備液；旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存式和期限：-80C, 6 months; -20C, 1 m

3、onth。-80C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?6 個(gè)內(nèi)使，-20C 儲(chǔ)存時(shí)，請(qǐng)?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥式選擇適當(dāng)?shù)娜芙獍?。以下溶解案都?qǐng)先按照 In Vitro 式配制澄清的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄 的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使； 以下溶劑前顯的百分 指該溶劑在您配制終溶液中的體積占；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的式助溶1. 請(qǐng)依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.60

4、 mM); Clear solution此案可獲得 2.5 mg/mL (6.60 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 400 L PEG300 中，混合均勻；向上述體系中加50 L Tween-80，混合均勻；然后繼續(xù)加 450 L 理鹽定容 1 mL。2. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (6.60 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5

5、 mg/mL (6.60 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合均勻。3. 請(qǐng)依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.60 mM); Clear solution此案可獲得 2.5 mg/mL (6.60 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個(gè)以上的實(shí)驗(yàn)。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲(chǔ)備液加到 900 L 油中，混合均

6、勻。BIOLOGICAL ACTIVITY物活性 Quinidine hydrochloride monohydrate 19.9 M。種抗律失常劑，也是K+ 通道 (K+ channel) 的有效阻斷劑，其 IC50 值為IC & Target IC50: 19.9 M (K+ channel)1體外研究 Quinidine hydrochloride monohydrate blocks WT mSlo3 (KCa5.1) channels with an IC50 of 19.91.41 M and Hillslope of 1.150.15 (n=7). Again, the pote

7、ncy of inhibition by Quinidine hydrochloride monohydrate is higher forF304Y mSlo3 (IC50 of 2.420.60 M, n=9, P0.005; Hill slope of 0.980.12), but lower with R196Q mSlo3 (IC50 of38.46.77 M, n=5, P0.001; Hill slope of 1.050.16). The inhibition of F304Y mSlo3 by Quinidine hydrochloridemonohydrate is obs

8、erved to have some time dependence1.體內(nèi)研究 Direct application of Quinidine hydrochloride monohydrate on the sciatic nerve produces a dose-related decrease inamplitude at ascending somato-sensory evoked potential (SSEP) and descending compound muscle action potentials (CMAP) when comparing baseline wit

9、h other time points, or when comparing the experimental left limb to the rightcontra-lateral glucose-treated limb. The latencies of SSEPs and CMAP potentials after Quinidine hydrochloridemonohydrate applications are increased compare to baseline and the contralateral side2.PROTOCOLCell Assay 1 Mouse

10、 (m) Slo3 (KCa5.1) channels or mutant forms are expressed in Xenopus oocytes and currents recorded with 2-electrode voltage-clamp. Gain-of-function mSlo3 mutations are used to explore the state-dependence of theinhibition. The interaction between Quinidine hydrochloride monohydrate and mSlo3 channel

11、s is modelled by insilico docking1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal 24 rats are randomly divided into three groups with eight rats in each group. Groups Q1, Q3, and Q5 receiveAdministration 2 Quinidine hydrochloride monohydrate 1,

12、3, and 5 mol, respectively, in 5 % glucose 0.1 mL. The sciatic nerve isexposed by making an incision from the left sciatic notch to the distal thigh. The subcutaneous tissue is bluntlydissected to expose the biceps femoris. The sciatic nerve is freed from its investing fascia. The procedure is thenr

13、epeated on the right side. The somato-sensory evoked potential (SSEP) and compound muscle action potentials(CMAP) are recorded at baseline, immediately after Quinidine hydrochloride monohydrate treatment, then every 15min thereafter for 1 h, then every 30 min thereafter for 3 h. The animals are allo

14、wed to recover and then keptseparately for 2 weeks. After performing behavioral examinations, electrophysiological examinations are performedwith the animals under intra-peritoneal anesthesia2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Page 2 of 3

15、www.MedChemE戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Environ Int. 2019 Jun;127:694-703. RSC Adv. 2019 May. Pharmacol Res Perspect. 2020 Apr;8(2):e00575.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Wrighton DC, et al. Mechanism of inhibition of mouse Slo3 (KCa 5.1) potassium channels by quinine, quinidine and barium. Br J Pharmacol. 2015Sep;172(17):4355-63.2. Cheng KI, et al. Application of quinidine on rat sciatic nerve decreases the amplitude and increases the latency of evoked responses. J Anesth. 2014Au