1104599-69-0
基本信息
MK4256,MK 4256
1H-Pyrido[3,4-b]indole, 3-[5-(4-fluorophenyl)-1H-imidazol-2-yl]-2,3,4,9-tetrahydro-1-(5-methyl-1,2,4-oxadiazol-3-yl)-1-(1-methyl-1H-pyrazol-4-yl)-, (1R,3R)-
物理化学性质
| 沸点 | 826.7±75.0 °C(Predicted) |
| 密度 | 1.52±0.1 g/cm3(Predicted) |
| 储存条件 | -20°C储存 |
| 溶解度 | DMSO : ≥ 100 mg/mL (202.22 mM);Water : < 0.1 mg/mL (insoluble) |
| 酸度系数(pKa) | 13.02±0.10(Predicted) |
| 形态 | Solid |
| 颜色 | Light yellow to yellow |
常见问题列表
IC50: 0.66 nM (human SSTR3), 0.36 nM (mouse SSTR3)
MK-4256 has excellent selectivity against other SSTR subtypes based on in vitro assays. In human receptor binding assays, MK-4256 has IC 50 s >2 μM for SSTR1 and SSTR2. Although the binding IC 50 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 IC 50 values are greater than 5 μM (at least 5000-fold selectivity). MK-4256 inhibits radiolabeled MK-499 binding of the hERG channel with an IC 50 =1.74 μM. In a functional patch clamp assay, MK-4256 exhibits 50% blockade of hERG at 3.4 μM concentration.
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 C max of MK-4256 is determined from parallel mouse PK studies. At 0.01, 0.1, and 1 mg/kg oral dose, MK-4256 achieves C max of 7, 88, and 493 nM, respectivley.