索馬魯肽三氟乙酸作用機(jī)制 - Medchemexpress - MCE中國

1、Product Data SheetSemaglutide TFACat. No.: HY-114118A分量: 4210.63作靶點(diǎn): Glucagon Receptor作通路: GPCR/G Protein儲存式: Powder -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) DMSO : 100 mg/mL (23.75 mM; Need ultrasonic)H2O : 0.1 mg/mL (insoluble)SolventMass1 mg 5 mg 10 mgConcentration制備儲備

2、液1 mM 0.2375 mL 1.1875 mL 2.3749 mL5 mM 0.0475 mL 0.2375 mL 0.4750 mL10 mM 0.0237 mL 0.1187 mL 0.2375 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。-80C 儲存時，請?jiān)?6 個內(nèi)使，-20C 儲存時，請?jiān)?1 個內(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 式配制澄清的儲備液，再依次添加助溶劑：

3、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 (0.59 mM); Clear solution此案可獲得 2.5 mg/mL (0.59 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 儲備液加到 400

4、 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 (0.59 mM); Suspended solution; Need ultrasonic此案可獲得 2.5 mg/mL (0.59 mM) 的均勻懸濁液，懸濁液可于服和腹腔注射。以 1 mL 作液為例，取 100 L 25.0 mg/mL 的澄 DMSO 儲備液加到 900 L 20% 的 SBE-CD 理鹽溶液中，混合P

5、age 1 of 2 www.MedChemE均勻。3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (0.59 mM); Clear solution此案可獲得 2.5 mg/mL (0.59 mM，飽和度未知) 的澄 溶液，此案不適于實(shí)驗(yàn)周 期在半個以上的實(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 Semaglutide TFA胰糖素樣肽-1 的個長效類似物， 胰糖素樣肽-1 (GLP-1) 受體激動劑

6、。Semaglutide TFA 有潛于 2 型糖尿病的研究。IC & Target GLP-1 receptor1.體外研究 Semaglutide has two amino acid substitutions compared to human GLP-1 (Aib8, Arg34) and is derivatized at lysine 26.The GLP-1R affinity of Semaglutide is 0.380.06 nM1. Semaglutide is a GLP-1 analogue with 94% sequence omologyto human GLP

7、-13.體內(nèi)研究 The plasma half-life of Semaglutide is 46h in mini-pigs following i.v. administration and semaglutide has an MRT of63.6h after s.c. dosing to mini-pigs1. Semaglutide improves 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-induced motor impairments. In addition, Semaglutide rescues the

8、 decrease of tyrosine hydroxylase (TH) levels,alleviates the inflammation response, reduces lipid peroxidation, inhibits the apoptosis pathway, and also increasesautophagy- related protein expression, to protect dopaminergic neurons in the substantia nigra and striatum.Moreover, the long-acting GLP-

9、1 analogue semaglutide is superior to liraglutide in most parameters2. Semaglutidelowers blood glucose by stimulating the release of insulin and also lowers body weight3.PROTOCOLAnimal Mice2Administration 2 Male C57BL/6 mice 10 weeks old (20-25 g) are used throughout the study. Mice are randomized d

10、ivided into sixgroups (n=12 per group) (i) control group treated with saline alone; (ii) liraglutide group treated with saline andliraglutide (25 nmol/kg ip. once daily for 7 days); (iii) Semaglutide group treated with saline and Semaglutide (25nmol/kg ip. once daily for 7 days), (iv) MPTP group tre

11、ated with MPTP alone (once daily 20 mg/kg ip. for 7 days); (v)MPTP (once daily 20 mg/kg ip. for 7 days) followed immediately by liraglutide treated group (25 nmol/kg ip. oncedaily for 7 days). (vi) MPTP (20 mg/kg ip. once daily for 7 days) followed immediately by Semaglutide treated group(25 nmol/kg

12、 ip. Once daily for 7 days). At the end of drug treatments, measure the behavioral changes, neuronaldamage, inflammatory markers, and other biomarkers2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Marso SP, et al. Semaglutide and Cardiov

13、ascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016 Nov 10;375(19):1834-1844.2. Zhang L, et al. Neuroprotective effects of the novel GLP-1 long acting analogue semaglutide in the MPTP Parkinsons disease mouse model.Neuropeptides. 2018 Oct;71:70-80.3. Dhillon S, et al. Semaglutide: First Global Approval. Drugs. 2018 Feb;78(2):275-284.Page 2 of 3 www.MedChemEMcePdfHeightCaution: Pr