MK-4101 is a Smoothened (SMO) antagonist (IC₅₀ of 1.1 µM for 293 cells ) and also a potent inhibitor of the hedgehog pathway (IC₅₀ of 1.5 µM for mouse cells; IC₅₀ of 1 µM for KYSE180 oesophageal cancer cells). MK-4101 has robust antitumor activity that inhibits tumor cell proliferation and induces extensive apoptosis^[1].

IC50: 1.1 µM (293 cells ); 1.5 µM (mouse cells); 1 µM (KYSE180 oesophageal cancer cells)^[1]

MK-4101 inhibits Hh signaling both in a reporter gene assay in an engineered mouse cell line with an IC₅₀ of 1.5 µM, and in human KYSE180 oesophageal cancer cells with an IC₅₀ of 1 µM. MK-4101 displaces a fluorescently-labeled cyclopamine derivative from 293 cells expressing recombinant human SMO with an IC₅₀ of 1.1 µM, implying that the compound binds to SMO. MK4101 also inhibits the proliferation of medulloblastoma cells derived from neonatallyirradiated Ptch1^-/+ mice in vitro with an IC₅₀ of 0.3 µM^[1].
MK-4101 (10 µM; 60 hours, 72 hours; medulloblastoma or BCC cells) treatment shows cell cycle arrest with a nearly complete disappearance of the S phase subpopulation, a prominent increase of the G1 population and, to a minor extent, of the G2 population^[1].
MK-4101 (10 µM; medulloblastoma or BCC cells) treatment significantly reduces cyclin D1 protein and accumulation of cyclin B1 protein^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

MK-4101 (40-80 mg/kg; oral administration; for 3.5 weeks; CD1 nude female mice) treatment shows tumor growth inhibition (40 and 80 mg/kg ) and tumor regression at the highest dose (80 mg/kg). MK-4101 treatment shows a dose-dependent down-regulation of Gli1 mRNA. The maximum effect for tumor inhibition and hedgehog pathway downregulation is achieved at 80 mg/kg^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

493.47

C₂₄H₂₄F₅N₅O

935273-79-3

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 50 mg/mL (101.32 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°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 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: ≥ 2.5 mg/mL (5.07 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.07 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 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% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.5 mg/mL (5.07 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.07 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (5.07 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.07 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 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Filocamo G et al. MK-4101, a Potent Inhibitor of the Hedgehog Pathway, Is Highly Active against Medulloblastoma and Basal Cell Carcinoma. Mol Cancer Ther. 2016 Jun;15(6):1177-89.