Setmelanotide-RM-493-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESetmelanotideCat. No.: HY-19870CAS No.: 920014-72-8Synonyms: RM-493; BIM-22493; IRC-022493分式: CHNOS分量: 1117.31作靶点: Melanocortin Receptor作通路: GPCR/G Protein; Neuronal Signaling储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 m

2、onths-20C 1 month溶解性数据体外实验 H2O : 24 mg/mL (21.48 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 0.8950 mL 4.4750 mL 8.9501 mL5 mM 0.1790 mL 0.8950 mL 1.7900 mL10 mM 0.0895 mL 0.4475 mL 0.8950 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。BIOLOGICAL ACTI

3、VITY物活性 Setmelanotide (RM-493; BIM-22493; IRC-022493)种质素 4 受体 (MC4R) 激动剂，作于和质素 4 受体，EC50 分别为 0.27 nM 和 0.28 nM 1。IC50 & Target Ki:3.9 nM (hMC1R), 10 nM (hMC3R), 2.1 nM (hMC4R), 430 nM (hMC5R), 2.7 nM (rMC4R) 1EC50: 5.8 nM (hMC1R), 5.3nM (hMC3R), 0.27 nM (hMC4R), 0.28 (rMC4R), 1600 nM (hMC5R) 11/2 Ma

4、ster of Small Molecules 您边的抑制剂师www.MedChemE体外研究 Melanocortin receptor agonists act in the brain to regulate food intake and body weight and, independently ofthese actions, affect insulin sensitivity. Setmelanotide exhibits agonist activity to human and rat MC4R withKis of 2.1 and 2.7 nM and EC50s of

5、 0.27 and 0.28 nM, respectively 1.体内研究 Inhibition of refeeding after an overnight fast by BIM-22493 is dependent on functional MC4R, and does notrequire MC3R. BIM-22493 acutely improves glucose homeostasis. Lepob/Lepob mice treated with BIM-22493 exhibits significantly improved glucose clearance whe

6、n compared to controls. Chronic BIM-22493treatment was associated with significantly lower levels of serum insulin, glucose and HOMA-IR values,suggesting an improvement in insulin sensitivity 1. Treatment with setmelanotide results in transientdecreases in food intake (35%), with persistent weight l

7、oss over 8 weeks of treatment (13.5%) in a diet-induced obese nonhuman primate model 2.PROTOCOLKinase Assay 1 Cell membranes are prepared from CHO-K1 cells stably expressing the human melanocortin receptorsubtypes (MC1R, MC3R, MC4R and MC5R). They are incubated at 1-10 g protein/well in 50 mM Tris-H

8、Cl,pH 7.4, containing 0.2% BSA, 5 mM MgCl2, 1 mM CaCl2 and 0.1 mg/mL bacitracin, with increasingconcentrations of setmelanotide and 0.1-0.3 nM 125I-NDP-MSH for 90-120 min at 37C, depending onthe receptor subtype. Bound from free 125I-NDP-MSH is separated by filtration through GF/C glass fiberfilters

9、 presoaked with 0.1 % (w/v) PEI. Filters are washed three times with 50 mM Tris-HCl, pH 7.4, at 0-4Cand assayed for radioactivity using Perkin Elmer Topcount scintillation counter 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: Mice are w

10、eighed. Baseline blood glucose is measured and 2 g/kg body weight of D-glucose injectedAdministration 1 by i.p. BIM-22493 is administered chronically at a dose of 300 nmol/kg/day for 14 days by sc. osmotic pump.Controls are administered with 0.9% saline during the same period. Blood glucose is measu

11、red at 15, 30, 60,and 120 minutes post injection 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 J Med Chem. 2017 Nov 9;60(21):8716-8730. Department od Analytical Chemistry, Charles University. 2019 Jun.See more customer validations on HYP

12、ERLINK / www.MedChemEREFERENCES1. Kumar KG, et al. Analysis of the therapeutic functions of novel melanocortin receptor agonists in MC3R- and MC4R-deficient C57BL/6Jmice. Peptides. 2009 Oct;30(10):1892-900.2. Kievit P, et al. Chronic treatment with a melanocortin-4 receptor agonist causes weight loss, reduces insulin resistance, and improvescardiovascular function in diet-induced obese rhesus macaques. Diabetes. 2013 Feb;62(2):490-7.McePdfHeight2/2 Master of Small Molecules 您边的抑制剂师www.MedChemEC