MK-4256-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEMK-4256Cat. No.: HY-13466CAS No.: 1104599-69-0分式: CHFNO分量: 494.52作靶点: Somatostatin Receptor作通路: GPCR/G Protein; Neuronal Signaling储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 100 mg/mL (

2、202.22 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 3 mg/mL (6.07 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 3 mg/mL (6.07 mM); Clear solution1/2 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 MK-4256种有效的选择性 SSTR3 拮抗剂。在和受体结合测定中，IC50 分别为 0.66 nM 和

3、0.36nM。IC50 & Target IC50: 0.66 nM (human SSTR3), 0.36 nM (mouse SSTR3) 1体外研究 MK-4256 has excellent selectivity against other SSTR subtypes based on in vitro assays. In human receptorbinding assays, MK-4256 has IC50s 2 M for SSTR1 and SSTR2. Although the binding IC50 values onSSTR4 and SSTR5 are bel

4、ow 1 M, there is still 500-fold selectivity. MK-4256 is tested in functionalantagonist assays against SSTR4 and SSTR5. The IC50 values are greater than 5 M (at least 5000-foldselectivity) 1. MK-4256 inhibits radiolabeled MK-499 binding of the hERG channel with an IC50=1.74 M. Ina functional patch cl

5、amp assay, MK-4256 exhibits 50% blockade of hERG at 3.4 M concentration 2.体内研究 MK-4256 reduces glucose excursion in a dose-dependent fashion with maximal efficacy achieves at dosesas low as 0.03 mg/kg po. MK-4256 demonstrates exceptional SSTR3-mediated glucose-lowering efficacy inthe mouse oGTT mode

6、l with minimal hypoglycemia risk. MK-4256 achieves complete ablation of glucoseexcursion (109%) at 1 mg/kg po. MK-4256 reduces the glucose excursion from 0.003 to 10 mg/kg in a dose-dependent manner. The plasma Cmax of MK-4256 is determined from parallel mouse PK studies. At 0.01,0.1, and 1 mg/kg or

7、al dose, MK-4256 achieves Cmax of 7, 88, and 493 nM, respectivley 1.PROTOCOLAnimal Mice 1Administration 1 To demonstrate that the observed glucose lowering by MK-4256 is SSTR3-dependent, the effect of amaximally efficacious dosage of MK-4256 on blood glucose excursion during an oGTT was investigated

8、 inSSTR3 KO mice. Administration of MK-4256 (1 mg/kg) and compound A (1 mg/kg; des-F-sitagliptin, a DPP-4inhibitor included as a positive control) to age-matched C57BL/6N male WT mice significantly inhibits bloodglucose excursion by 112 and 91%, respectively.MCE has not independently confirmed the a

9、ccuracy of these methods. They are for reference only.REFERENCES1. He S, et al. The Discovery of MK-4256, a Potent SSTR3 Antagonist as a Potential Treatment of Type 2 Diabetes. ACS Med Chem Lett.2012 May 7;3(6):484-9.2. He S, et al. Investigation of Cardiovascular Effects of Tetrahydro-carboline sstr3 antagonists. ACS Med Chem Lett. 2014 Apr21;5(7):748-53.McePdfHeightCaution: Product has not been fully validated for me