MK-4256 is a potent and selectiveSSTR3antagonist withIC₅₀s of 0.66 nM and 0.36 nM in human and mouse receptor binding assays, respectively.

IC50: 0.66 nM (human SSTR3), 0.36 nM (mouse SSTR3)^[1]

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 IC₅₀values 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 IC₅₀values are greater than 5 μM (at least 5000-fold selectivity)^[1]. 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^[2].

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_maxof MK-4256 is determined from parallel mouse PK studies. At 0.01, 0.1, and 1 mg/kg oral dose, MK-4256 achieves C_maxof 7, 88, and 493 nM, respectivley^[1].

494.52

Solid

C₂₇H₂₃FN₈O

1104599-69-0

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 100 mg/mL(202.22 mM)

*"≥" means soluble, but saturation unknown.

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；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: ≥ 3 mg/mL (6.07 mM); Clear solution

  此方案可获得 ≥ 3 mg/mL (6.07 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 30.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液
• 2.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: ≥ 3 mg/mL (6.07 mM); Clear solution

  此方案可获得 ≥ 3 mg/mL (6.07 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 30.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。