MK-4256 has excellent selectivity against other SSTR subtypes based on in vitro assays. In human receptor binding assays, MK-4256 has IC50s >2 μM for SSTR1 and SSTR2. Although the binding IC50 values on SSTR4 and SSTR5 are below 1 μM, there is still >500-fold selectivity. MK-4256 is tested in functional antagonist assays against SSTR4 and SSTR5. The IC50 values are greater than 5 μM (at least 5000-fold selectivity). MK-4256 inhibits radiolabeled MK-499 binding of the hERG channel with an IC50=1.74 μM. In a functional patch clamp assay, MK-4256 exhibits 50% blockade of hERG at 3.4 μM concentration.
体内研究
MK-4256 reduces glucose excursion in a dose-dependent fashion with maximal efficacy achieves at doses as low as 0.03 mg/kg po. MK-4256 demonstrates exceptional SSTR3-mediated glucose-lowering efficacy in the mouse oGTT model with minimal hypoglycemia risk. MK-4256 achieves complete ablation of glucose excursion (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 oral dose, MK-4256 achieves Cmax of 7, 88, and 493 nM, respectivley.
分子式
C27H23FN8O
分子量
494.52
CAS号
1104599-69-0
运输条件
Room temperature in continental US; may vary elsewhere.