卡格列凈作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetCanagliflozinCat. No.: HY-10451CAS No.: 842133-18-0分式: CHFOS分量: 444.52作靶點(diǎn): SGLT作通路: Membrane Transporter/Ion Channel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 : 50 mg/mL (112.48 mM)* means soluble, but saturation unknown.SolventMass1 mg 5 m

2、g 10 mgConcentration制備儲(chǔ)備液1 mM 2.2496 mL 11.2481 mL 22.4962 mL5 mM 0.4499 mL 2.2496 mL 4.4992 mL10 mM 0.2250 mL 1.1248 mL 2.2496 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 month。-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)娜芙獍浮Ｒ韵氯芙獍付颊?qǐng)先按照 In

3、 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；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/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 (5.62 mM); Clear solution此案可獲得 2.5 mg/mL (5.62 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，取 100 L 25

4、.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 (5.62 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (5.62 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

5、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 (5.62 mM); Clear solution此案可獲得 2.5 mg/mL (5.62 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，混合均勻。BIOLOGICAL ACTIVITY物活性 Canagliflozin (JNJ 28431754)種選擇性的 SGLT2 抑制劑，作于表達(dá) mSGLT2

6、，rSGLT2 和 hSGLT2 的 CHO細(xì)胞，IC50 分別為 2 nM，3.7 nM 和 4.4 nM1。IC & Target IC50: 2/3.7/4.4 nM (mSGLT2/rSGLT2/hSGLT2, in CHOK cells)1體外研究 Canagliflozin inhibits Na+-dependent 14C-AMG uptake in CHO-hSGLT2 cells, with an IC50 of 4.41.2 nM. Similar IC50values are obtained in CHO-rSGLT2 and CHO-mSGLT2 cells (IC

7、50 = 3.7 and 2.0 nM for rat and mouse SGLT2,respectively). Canagliflozin inhibits 14C-AMG uptake in CHO-hSGLT1 and mSGLT1 cells with IC50 of 684159 nM and1,000 nM, respectively1.體內(nèi)研究 Canagliflozin (30 mg/kg treatment for 4 weeks) reduces blood glucose (BG) levels, respiratory exchange ratio, andbody

8、 weight gain in DIO mice1.Canagliflozin (3 mg/kg for 3 weeks) increases urinary glucose excretion (UGE) with no significant change in total foodintake compared with that in vehicle-treated rats, leading to a decrease in body weight In ZF rats1.Animal Model: Diet-induced obese, insulin resistantmice

9、(DIO) Mice1Dosage: 30 mg/kgAdministration: Oral gavage; daily; 4 weeksResult: Reduced BG levels, respiratory exchange ratio, and body weight gain.Animal Model: Male Zucker fatty (ZF) obese, insulin resistant rats1Dosage: 3 mg/kgAdministration: Oral gavage; daily; 3 weeksResult: UGE was increased wit

10、h no significant change in total food intake compared with thatin vehicle-treated rats, leading to a decrease in body weight.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Nature. 2018 Aug;560(7719):499-503. Mol Metab. 2019 Jan;19:1-12. Biochem Pharmacol. 2020 Feb 13:113856.Page 2 of 3 www.MedChemE Biochem Pharmacol. 2018 Jun;152:45-

11、59. Vascul Pharmacol. 2018 Oct;109:56-71.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Liang Y, et al. Effect of canagliflozin on renal threshold for glucose, glycemia, and body weight in normal and diabetic animal models. PLoS One.2012;7(2):e30555.McePdfHeightCaution: Product has not been fully validated