Mirdametinib (PD0325901) 是一种具有口服活性,选择性和非 ATP 竞争性的MEK抑制剂,IC50为 0.33 nM。Mirdametinib 对活化的 MEK1 和 MEK2 的Kiapp值为 1 nM。Mirdametinib 抑制 p-ERK1/2 的表达并诱导细胞凋亡 (apoptosis)。Mirdametinib 对多种人类肿瘤异种移植物具有抗癌活性。
生物活性 | Mirdametinib (PD0325901) is an orally active, selective and non-ATP-competitiveMEKinhibitor with anIC50of 0.33 nM. Mirdametinib exhibits aKiappof 1 nM against activatedMEK1andMEK2. Mirdametinib suppresses the expression of p-ERK1/2 and inducesapoptosis. Mirdametinib has anti-cancer activity for a broad spectrum of human tumor xenografts[1][2][3]. |
IC50& Target[1][2] | MEK1 1 nM (Ki) | MEK2 1 nM (Ki) | MEK 0.33 nM (IC50) |
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体外研究 (In Vitro) | Mirdametinib (PD325901; 0.0064, 0.032, 0.16, 0.8, 4, 20, 100 nM; for 2 days) inhibits the growth of Papillary thyroid carcinomas (PTC) cell lines (TPC-1 cells and K2 cells) with GC50of 11 nM and 6.3 nM, respectively[3]. Mirdametinib (100 nmol/L; for 4 days) induces apoptosis in K2 cells (top) or TPC-1 cells[3]. Mirdametinib (0.1, 1, 10, 100, 1000 nM; for 1 hour) suppresses the expression of p-ERK1/2 in K2 cells (top) or TPC-1 cells[3]. Mirdametinib prevents the growth of melanoma cell lines. Mirdametinib significantly prevents the the growth of PTC cells harboring a BRAF mutation at very low concentration (10 nM)[3].
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体内研究 (In Vivo) | Mirdametinib (25 mg/kg, p.o.) inhibits phosphorylation of ERK by more than 50% at 24 hours post-dosing. Mirdametinib (25 mg/kg/day; po) produces a 70% incidence of complete tumor responses (C26 model)[2]. Mirdametinib (20-25 mg/kg/day; oral gavage; for 3 weeks (5 consecutive days/week)) suppresses tumor growth completely in mice inoculated with PTC cells carrying a BRAF mutation (K2) and significantly decreased tumor growth in mice inoculated with PTC cells carrying the RET/PTC1 rearrangement (TPC-1) in athymic Ncr-nu/nu mice at ages 6 to 8 weeks[3].
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : ≥ 56 mg/mL(116.14 mM) *"≥" means soluble, but saturation unknown. 配制储备液 1 mM | 2.0739 mL | 10.3694 mL | 20.7387 mL | 5 mM | 0.4148 mL | 2.0739 mL | 4.1477 mL | 10 mM | 0.2074 mL | 1.0369 mL | 2.0739 mL |
*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。 In Vivo: 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: ≥ 2.08 mg/mL (4.31 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.31 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 20.8 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。 2. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.08 mg/mL (4.31 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.31 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 3. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (4.31 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.31 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 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。 *以上所有助溶剂都可在本网站选购。
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