艾塞那肽作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetExendin-4Cat. No.: HY-13443CAS No.: 141758-74-9分式: CHNOS分量: 4186.57Sequence: His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2Sequence Shortening: HGEGTFTSDLSKQMEEEAVRLFIEW

2、LKNGGPSSGAPPPS-NH2作靶點(diǎn): Glucagon Receptor作通路: GPCR/G Protein儲存式: Protect from lightPowder -80C 2 years-20C 1 yearIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) H2O : 50 mg/mL (11.94 mM)DMSO : 32 mg/mL (7.64 mM)* means soluble, but saturation unknown.SolventMass1 mg 5 mg 10 mgConcentration制備儲備液1 mM 0.2

3、389 mL 1.1943 mL 2.3886 mL5 mM 0.0478 mL 0.2389 mL 0.4777 mL10 mM 0.0239 mL 0.1194 mL 0.2389 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；旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存式和期限：-80C, 6 months; -20C, 1 month (protect from light)。-80C 儲存時(shí)，請?jiān)?6 個(gè)內(nèi)使，-20C 儲存時(shí)，請?jiān)?1 個(gè)內(nèi)使。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動物和給藥式選擇適當(dāng)?shù)娜芙獍浮Ｒ韵氯芙獍付颊埾劝凑?In Vitro 式配制澄清的儲

4、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 的儲備液可以根據(jù)儲存條件，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. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (0.60 mM); Clear solutionPage 1 of 2 www.MedChemE此案可獲得 2.5 mg/mL (0.60 mM，飽和度未知) 的澄清溶液。以 1 mL 作液為例，

5、取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 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. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (0.60 mM); Clear solution此案可獲得 2.5 mg/mL (0.60 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 的澄均勻。DMSO 儲備液加到 900 L 20% 的 SBE-CD

6、 理鹽溶液中，混合3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (0.60 mM); Clear solution此案可獲得 2.5 mg/mL (0.60 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 儲備液加到 900 L 油中，混合均勻。BIOLOGICAL ACTIVITY物活性 Exendin-4 (Exenatide)是由 39 個(gè)氨基酸組成的多肽。它是長效的 glucagon-like peptide-1 受體激

7、動劑，IC50 值為 3.22 nM。IC & Target IC50: 3.22 nM (glucagon-like peptide-1 receptor)1體外研究 In human umbilical vein endothelial cells, exendin-4 significantly increases NO production, endothelial NO synthase(eNOS) phosphorylation, and GTP cyclohydrolase 1 (GTPCH1) level in a dose-dependent manner2. Exendin

8、-4 showscytotoxic effects to MCF-7 breast cancer cells with IC50 of 5 M at 48 hour3.體內(nèi)研究 Both low- and high-dose exendin-4 treatment in ob/ob mice improve serum ALT and reduce serum glucose, andcalculated HOMA scores compared with control. Exendin-4-treated ob/ob mice sustain a marked reduction in t

9、he netweight gain in the final 4 weeks of the study period4. Animals treated with exendin-4 have more pancreatic acinarinflammation, more pyknotic nuclei and weigh significantly less than control rats. Exendin-4 treatment is associatedwith lower leptin levels as well as lower HOMA values in rats5. E

10、xenatide causes dose-dependent relaxation of ratthoracic aorta, which is evoked via the GLP-1 receptor and is mediated mainly by H2S but also by NO and CO6.PROTOCOLAnimal Rats: 20 Sprague-Dawley male rats, ten of which are treated with exendin-4 (10 g/kg) and ten of which are used asAdministration 4

11、5 controls. The study period is 75 days. Serum and pancreatic tissue are removed for biochemical and histologicalstudy. Blood glucose, amylase, lipase and adipocytokines are compared between the two groups5.Mice: The exendin-4 treatment groups are treated with 10 g/kg every 24 hours for the first 14

12、 days. This treatmentis the induction phase. Respective control mice (lean and ob/ob) receive saline every 24 hours. After 14 days Exendin-4-treated mice are randomly divided into two groups: one group receives high dose exendin-4 (20 g/kg) every 12hours, while the second group continues with low do

13、se exendin-4 (10 g/kg) every 12 hours. The control micecontinue to receive saline every 12 hours. The mice are weighed daily for the 60-day treatment period4.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Page 2 of 3 www.MedChemE戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Br J Pharma

14、col. 2020 Mar 30. J Neuroinflammation. 2019 Nov. J Biol Chem. 2018 Nov 23;293(47):18086-18098. Sci Rep. 2017 Jun 28;7(1):4351. Front Pharmacol. 2019 Oct 25;10:1230.See more customer validations on HYPERLINK www.MedChemE www.MedChemEREFERENCES1. Doyle ME, et al. The importance of the nine-amino acid

15、C-terminal sequence of exendin-4 for binding to the GLP-1 receptor and for biological activity.Regul Pept. 2003 Jul 15;114(2-3):153-8.2. Wei R, et al. Exenatide exerts direct protective effects on endothelial cells through the AMPK/Akt/eNOS pathway in a GLP-1 receptor-dependent manner.Am J Physiol E

16、ndocrinol Metab. 2016 Jun 1;310(11):E947-57.3. Fidan-YaylalI G, et al. Antidiabetic exendin-4 activates apoptotic pathway and inhibits growth of breast cancer cells. Tumour Biol. 2016 Feb;37(2):2647-53.4. Ding X, et al. Exendin-4, a glucagon-like protein-1 (GLP-1) receptor agonist, reverses hepatic

17、steatosis in ob/obmice. Hepatology. 2006 Jan;43(1):173-81.5. Nachnani JS, et al. Biochemical and histological effects of exendin-4 (exenatide) on the rat pancreas. Diabetologia. 2010 Jan;53(1):153-9.6. Selley E, et al. Exenatide induces aortic vasodilation increasing hydrogen sulphide, carbon monoxide and nitric oxide production.