Trametinib (GSK1120212)是一种高特异性的，有效的MEK1/2抑制剂，IC50为0.92 nM/1.8 nM，对c-Raf， B-Raf， ERK1/2没有抑制活性。
别名：JTP-74057, GSK212
Trametinib (GSK1120212)是一种高特异性的，有效的MEK1/2抑制剂，IC50为0.92 nM/1.8 nM，对c-Raf， B-Raf， ERK1/2没有抑制活性。GSK1120212抑制 MBP 的磷酸化，对于不同亚型的Raf和MEK 而言，IC50在0.92 nM-3.4 nM。GSK1120212对c-Raf, B-Raf, ERK1和ERK2的激酶活性没有抑制作用。另外，GSK1120212对于其它98种激酶没有很强的抑制作用。
Immunobiology. 2023 Jan;228(1):152311.
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Cancer Cell. 2018 Sep 10;34(3):411-426.e19.
Int J Mol Sci. 2018 Jan 18;19(1) pii: E289.
Biochem Pharmacol. 2015 Aug 15;323-36.
J Biol Chem. 2014 Sep 26;289(39):27090-104.
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数据来源 | Cancer Cell (2018). Figure 5. Trametinib (Abmole Bioscience, Houston, USA) |
| 方法 | oral gavage | |
| 细胞系/动物模型 | Mice | |
| 浓度 | 0.1 mg/kg | |
| 处理时间 | — | |
| 实验结果 | Mice treated with IRN + VCR had stable disease (SD), whereas mice treated with either palbociclib + trametinib or abemaciclib + trametinib exhibited progressive disease. |
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数据来源 | Int J Mol Sci (2018). Figure 5. GSK1120212 (AbMole BioScience, Houston, TX, USA) |
| 方法 | vitro experiments | |
| 细胞系/动物模型 | CAR-T cells | |
| 浓度 | 30 nM | |
| 处理时间 | 16 h | |
| 实验结果 | CAR-T cells in the conditions without inhibitor, with DMSO solvent control, with Vem alone, Tram alone, Dabra alone, and the combination Dabra + Tram |
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数据来源 | Int J Mol Sci (2018). Figure 4. GSK1120212 (AbMole BioScience, Houston, TX, USA) |
| 方法 | vitro experiments | |
| 细胞系/动物模型 | CAR-T cells | |
| 浓度 | 30 nM | |
| 处理时间 | 16 h | |
| 实验结果 | The presence of Vem alone, Tram alone,Cobi alone, Vem + Cobi, and Dabra + Tram, but not of Dabra alone seemed to reduce these quantities to approximately 50%. |
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数据来源 | Int J Mol Sci (2018). Figure 3. GSK1120212 (AbMole BioScience, Houston, TX, USA) |
| 方法 | vitro experiments | |
| 细胞系/动物模型 | CAR-T cells | |
| 浓度 | 30 nM | |
| 处理时间 | 16 h | |
| 实验结果 | The condition with Vem + Cobi was similarly inhibited as Vem alone, while the Dabra + Tram condition was significantly less inhibited |
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数据来源 | Int J Mol Sci (2018). Figure 2. GSK1120212 (AbMole BioScience, Houston, TX, USA) |
| 方法 | vitro experiments | |
| 细胞系/动物模型 | CAR-T cells | |
| 浓度 | 30 nM | |
| 处理时间 | 16 h | |
| 实验结果 | Incubation with the MEK inhibitors Tram and Cobi alone, but also the combination of Vem + Cobi reduced the CD25 upregulation approximately to 50% |
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数据来源 | Biochem Pharmacol (2015). GSK1120212, Figure 5. (Abmole Bioscience Kowloon, Hong Kong, China) |
| 方法 | western blot | |
| 细胞系/动物模型 | CD4+ T cells | |
| 浓度 | 20 mM | |
| 处理时间 | 24 h | |
| 实验结果 | Addition of GSK1120212, an inhibitor of MEK to the growth media diminished phosphorylation of ERK, but showed no noticeable effect on the inhibition of arctigenin against mTORC1 activation (Fig. 5D). |
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数据来源 | J Bio Chem (2014). Figure 9. GSK1120212 (AbMole BioScience). |
| 方法 | Rats in the inhibitor groups were treated with GSK1120212 | |
| 细胞系/动物模型 | ||
| 浓度 | 0.3 mg/kg | |
| 处理时间 | ||
| 实验结果 | In animals receiving GSK1120212, shockwave treatment did not significantly change the percentage of Ki-67 or phospho-Erk1/2 positive cells (Figure 9B and C). These data support our findings that ischemic wound healing in shockwave treated animals is significantly enhanced by shockwave treatment and is dependent on Erk1/2 pathways. |
. figure 8..jpg) |
数据来源 | J Bio Chem (2014). Figure 8. GSK1120212 (AbMole BioScience). |
| 方法 | Rats in the inhibitor groups were treated with GSK1120212 | |
| 细胞系/动物模型 | ||
| 浓度 | ||
| 处理时间 | ||
| 实验结果 | "Planimetric analysis of the wound size area on the ischemic side of the epigastric flap was performed immediately after surgery (day 0) and on days 1, 5, and 10 after surgery (Figure 8C and D) Shockwave treatment of the ischemic side of the epigastric flap (100 pulses at 0.13 mJ/mm2) significantly decreased the wound size compared to control animals (Figure 8A). In animals receiving the Mek1/2 inhibitor GSK1120212 (0.1 mg/kg daily), wound sizes in the control and shockwave groups did not differ (Figure 8B). These results suggest that shockwave treatment exerts its beneficial effects on wound healing by induction of Erk1/2 signaling." |
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数据来源 | Biochemical Pharmacology (2015). Figure 7. LY294002, MK-2206 and GSK1120212 were gifts from Abmole Bioscience (Kowloon, Hong Kong). |
| 方法 | Western blot | |
| 细胞系/动物模型 | Purified CD4+ T cells | |
| 浓度 | 20 mM LY294002, 10 mM MK-2206 as well as 10 mM GSK1120212 | |
| 处理时间 | 3 h | |
| 实验结果 | Arctigenin could inhibit mTORC1 activation via a way independent of PI3K/AKT and ERK. |
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数据来源 | J. Biol. Chem (2015). Figure 1. GSK1120212 (AbMole BioScience) |
| 方法 | IHC | |
| 细胞系/动物模型 | none | |
| 浓度 | 0.1 mg/kg daily | |
| 处理时间 | 10 days | |
| 实验结果 | Ischemic wound healing in shockwave treated animals is significantly enhanced by shockwave treatment and is dependent on Erk1/2 pathways. |
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数据来源 | J. Biol. Chem (2015). Figure 8. GSK1120212 (AbMole BioScience) |
| 方法 | shockwave treatment in vivo | |
| 细胞系/动物模型 | control | |
| 浓度 | 0.1 mg/kg daily | |
| 处理时间 | 10 days | |
| 实验结果 | Shockwave treatment enhances wound healing in a rat model by promoting proliferation via Erk1/2 signaling |
| 体外实验* | |
|---|---|
| 细胞系 | DO4, MM415, MM485, SK-MEL-2, MaMel30I and MaMel27II |
| 方法 | cells were plated in 96-well plates with a density of 4000-8000 cells per well and incubated for 24 h at 37 °C with 5% C02. Then cells were incubated with increasing drug concentrations and their combinations. Cell viability was measured with the CellTiter-Glo (CTG) Luminescent Cell Viability Assay (Promega; Madison, Wisconsin, USA) according to the manufacturer’s protocol. Luminescence was measured on the SynergyHT plate reader (BioTek, Vermont, USA) using Gen5 software (Version 1.11.5). For apoptotic assays, cells were plated in 12-well plates and treated with DMSO, trametinib, metformin or combinations. After 72hrs apoptosis was assessed using the Dead Cell Apoptosis Kit with Annexin V Alexa Fluor 488 & Propidium Iodide according to the manufacturer’s protocol (Invitrogen; V13241) with the AccuriC6 Flow Cytometer using the CFlow software (Version 1.0.227.4). |
| 浓度 | 0.2-30nM |
| 处理时间 | 72 h |
*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。
| 体内实验* | |
|---|---|
| 动物模型 | Tumor induction on the skin of the Tyr::CreERT2; PtenLoxP/LoxP;BrafCA/+ mice |
| 配制 | dissolved in 0.5% hydroxypropyl methylcellulose (Sigma-Aldrich) and 0.2% Tween-80 (Sigma-Aldrich) |
| 剂量 | 0.75 mg/kg, once daily |
| 给药处理 | orally |
*上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。
| 分子量 | 615.39 |
| 分子式 | C26H23FIN5O4 |
| CAS号 | 871700-17-3 |
| 溶解性（25°C） | DMSO 30 mg/mL |
| 储存条件 |
粉末型式 -20°C 3年；4°C 2年 溶于溶剂 -80°C 6个月；-20°C 1个月 |
| 运输方式 | 冰袋运输，根据产品的不同，可能会有相应调整。 |
*下述溶液配置方法仅为基于分子量计算出的理论值。不同产品在配置溶液前，需考虑其在不同溶剂中的溶解度限制。
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.625 mL | 8.1249 mL | 16.2499 mL |
| 5 mM | 0.325 mL | 1.625 mL | 3.25 mL |
| 10 mM | 0.1625 mL | 0.8125 mL | 1.625 mL |
| 小鼠 | 大鼠 | 兔 | 豚鼠 | 仓鼠 | 狗 | |
| 重量 (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| 体表面积 (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km 系数 | 3 | 6 | 12 | 8 | 5 | 20 |
| 动物 A (mg/kg) = 动物 B (mg/kg) × | 动物 B的Km系数 |
| 动物 A的Km系数 |
例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。
| 其他相关的MEK产品 |
|---|
| Glycinexylidide
Glycinexylidide (GX) 是 Lidocaine 的活性代谢物。 |
| Xantocillin
Xantocillin (Xanthocillin X) 是从青霉中提取的一种海洋药剂，通过抑制 MEK/ERK 途径诱导自噬。 |
| MEK-IN-6 hydrate
MEK-IN-6 hydrate 是一种 MEK 抑制剂。 |
| MS934
MS934 是一种新型改进的 VHL 招募 MEK 1/2 降解剂。 |
| Nedometinib
Nedometinib 是一种针对 MEK1 的酪氨酸激酶抑制剂。 |
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