1104599-69-0

中文名称化合物 T16095

英文名称 MK4256

CAS 1104599-69-0

分子式 C27H23FN8O

分子量 494.52

MOL 文件 1104599-69-0.mol

1104599-69-0 结构式

基本信息物理化学性质常见问题列表

基本信息

中文别名

化合物 T16095

英文别名

MK4256
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

生物活性

MK-4256 是一种有效的选择性 SSTR3 拮抗剂。在人和小鼠受体结合测定中，IC50 分别为 0.66 nM 和 0.36 nM。

靶点

IC50: 0.66 nM (human SSTR3), 0.36 nM (mouse SSTR3)

体外研究

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.

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 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.