目录号：S2673 别名： JTP-74057
Molecular Weight(MW): 615.39
Trametinib (GSK1120212)是一种高特异性的，有效的MEK1/2抑制剂，无细胞试验中IC50为0.92 nM/1.8 nM，对c-Raf， B-Raf， ERK1/2没有抑制活性。
SMYD3 knockout augments the effects of the MEK1/2 inhibitor Trametinib (GSK1120212) in vivo. Representative serial HE staining and IHC for pERK1/2, a marker of Ras activity, and MUC5, a marker of PanIN lesions. All scale bars, 50 um.
Nature 2014 510(7504), 283-7. Trametinib (GSK1120212) purchased from Selleck.
Immunofluorescence of E-cadherin, vimentin and DAPI in cells from grown on chamber slides and treated with 100 nM GSK1120212/trametinib. Scale bars represent 50 um.
Cancer Discov 2014 4(2), 232-45. Trametinib (GSK1120212) purchased from Selleck.
ERK phosphorylates FBW7 at T205. PANC-1 cells were pretreated with the proteasome inhibitor MG132 and trametinib, as indicated, overnight before harvest. Endogenous FBW7 phosphorylation status was examined by immunoblot analysis after immunoprecipitates (IP).
Cell Res 2015 25(5), 561-73. Trametinib (GSK1120212) purchased from Selleck.
MEK2C125S, but not the equivalent MEK1C121S variant, confers robust resistance to dabrafenib and trametinib. Transduced SKMel28 cells were seeded at low density and 24h after seeding were treated with the indicated concentrations of dabrafenib and trametinib every 72-96h. Colonies were stained with crystal violet 10 days post transduction. Photographs are representative of at least two independent transduction experiments.
Nat Commun 2015 5, 5694. Trametinib (GSK1120212) purchased from Selleck.
Ras, MEK and ERK control bronchial epithelial gene expression. Acute versus chronic GSK1120212. Acute (left panels): cells were seeded sparsely and incubated for 4 days in normal media and then subjected to a calcium switch and recovery, in the presence of DMSO (panel 1) or 500 nM GSK1120212 (panel 2). Chronic (right panels): cells were seeded sparsely and incubated for 4 days in DMSO (panel 3) or 500 nM GSK1120212 (panel 4). Cells were subjected to a calcium switch and recovery, in the presence of DMSO (panel 3) or 500 nM GSK1120212 (panel 4). Cells were fixed and stained for ZO-1 and DNA. Scale bar, 20 um.
EMBO Rep 2015 16(1), 87-96. Trametinib (GSK1120212) purchased from Selleck.
RDEA119 (1 uM) or JTP-74057 (0.1 uM) abolished the effects of G1 on DAPK1 and NR2B phosphorylation. The data were pooled from five independent experiments.
J Neurosci 2012 32, 4887-900. Trametinib (GSK1120212) purchased from Selleck.
Phosphorylation level of ERK1/2 and apoptosis after GSK1120212 exposure. Phosphorylation levels of ERK1/2 after GSK1120212 exposure. When the phosphorylation levels were examined after GSK1120212 exposure (0, 1, 3, 10, and 30 nM), the samples were collected 3 hours after the stimulation. GSK1120212 induced a significant decrease in the phosphorylation levels of ERK1/2 in the hypersensitive cell lines (OCUM-1 and Okajima), compared with that in the non-sensitive cell line (SNU-16). b-actin was used as an internal control.
Mol Cancer Ther 2014 13(12), 3098-106. Trametinib (GSK1120212) purchased from Selleck.
Dose response curve of compound on melanoma cell lines. Compound was dissolved in DMSO, added in a 5-fold dilution series, starting with 5μM, and incubated for 72 hours. Fluorescence was measured after 8 hours incubation in resazurin. Data was normalized to DMSO (maximal viability) and Doxorubicin (minimum viability).
One customer. Trametinib (GSK1120212) purchased from Selleck.
Figure 3 Anti-ErbB3 mAb A4 counteracts the increase of ErbB3-dependent AKT phosphorylation and potentiate growth inhibition
induced by GSK1120212b. (a) LOX IMVI melanoma cells were serum starved and treated with vemurafenib (0.3 μM), with GSK1120212b (GSK, 0.15 μ M) or with their combination in presence or not of anti-ErbB3 mAb A4 (20 μ g/ml) for 24 h. Western blot analysis shows that A4 mAb abrogate ErbB3 phosphotylation as well as the strong increase of pAKT induced by both inhibitors . For densitometric analysis pErbB3/ErbB3, pERK/ERK and pAKT/ATK values are expressed as fold change with respect to the control unstimulated cells to which value = 1 was assigned. Results are expressed as mean values from three independent experiments. (b) Cells were grown in the presence of different doses of GSK combinated or not with A4 mAb (20 μ g/ml) for 10 day. Cells were then dissolved in a Methanol/SDS solution and the adsorbance (595 nm) was read as above. Quantitative analysis for curve fitting and for IC50 evaluation, performed as above, shows that the treatment with A4 enhances the inhibitory effect of GSK on cell growth (IC50 GSK = 115 nM; IC50 GSK + A4 = 19 nM). p-values were calculated and significance level has been defined as above. For IC50 GSK + A4 p < 0,001 vs IC50 GSK. (c) Cells were treated with suboptimal doses of vemurafenib, GSK or their combination in presence or not of A4 mAb (c). The in vitro colony formation assay shows that the addition of A4 significantly inhibits cells growth. *p < 0,01 vs vem-treated or GSK-treated cells; ** p < 0,001 vs vem + GSK- treated cells; NS vs untreated cells.
Trametinib (GSK1120212) purchased from Selleck.
Mouse carcinoma cells were treated with the inhibitors for 16 and 40 h at the concentrations indicated. The effect on S-phase was evident at 16 hrs. (A) whereas apoptosis was induced at 40h. (B) Biological effects of the compounds correlated with effects on phosphorylation of the MEK target ERK. (C) IC50 on S-phase and ERK-posphorylation: TAK-733=1-10nM, GSK1120212=<1nM.
Jonas Nilsson, PhD from University of Gothenburg. Trametinib (GSK1120212) purchased from Selleck.
|产品描述||Trametinib (GSK1120212)是一种高特异性的，有效的MEK1/2抑制剂，无细胞试验中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。GSK1120212对于人结肠癌细胞系有很强的抑制作用，其中HT-29和COLO205细胞组成型表达有活性的B-Raf突变，这两种细胞对GSK1120212最为敏感，IC50分别是0.48 nM 和 0.52 nM。含有k-Raf突变的细胞系对GSK1120212的敏感性介于如下范围，IC50是2.2-174 nM. 相反地，COLO320 DM细胞中B-Raf 和K-Ras均为野生型，因而即便在10 μM都对GSK1120212有抗性。用GSK1120212处理24小时可以诱导所有敏感细胞的细胞周期停滞在G1期。与此一致，GSK1120212处理使得大部分人结肠癌细胞系中p15INK4b 和/或p27KIP1的表达量上升。GSK1120212能诱导HT-29和COLO205细胞的凋亡，COLO205细胞更为敏感。 GSK1120212抑制外周血单核细胞产生肿瘤坏死因子-α和白介素-6。 
|体内研究||按0.3 mg/kg或1 mg/kg 的剂量口服GSK1120212（一天一次共14天）能有效抑制HT-29肿瘤，1 mg/kg 的剂量可完全抑制肿瘤生长。在癌症组织中，一次口服1 mg/kg GSK1120212能完全抑制ERK1/2的磷酸化，14天后能提高p15INK4b和p27KIP1的表达量。在COLO205肿瘤模型中，0.3 mg/kg剂量的GSK1120212就足以抑制肿瘤生长，1 mg/kg剂量的GSK1120212可以使2/3的老鼠的肿瘤消退至可检测水平之下。 0.1 mg/kg剂量的GSK1120212完全抑制佐剂性关节炎(AIA)和II型胶原诱导的关节炎(CIA) Lewis大鼠或DBA1/J小鼠。|
Raf-MEK-ERK级联激酶检测:非磷酸化的髓鞘碱性蛋白（MBP）涂覆到ELISA板上，B-Raf/c-Raf的活性形式与非磷酸化MEK1/MEK2和ERERK2混合在10 μM ATP和12.5 mM MgCl2，其MOPS缓冲液中含有不同浓度的GSK1120212。 MBP的磷酸化是由抗磷酸化的MBP抗体进行检测。
|体外||DMSO||22 mg/mL warmed (35.74 mM)|
4% DMSO+corn oil
质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)
*在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。
开始浓度 x 开始体积 = 最终浓度 x 最终体积
稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )
在配置溶液时，请务必参考Selleck产品标签上、MSDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。.
|NCT Number||Recruitment||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT01723202||Active, not recruiting||Follicular Thyroid Cancer|Insular Thyroid Cancer|Papillary Thyroid Cancer|Recurrent Thyroid Cancer||Manisha Shah|National Comprehensive Cancer Network|Ohio State University Comprehensive Cancer Center||November 7, 2012||Phase 2|
|NCT02672358||Not yet recruiting||Non-Small-Cell Lung Cancer||Novartis Pharmaceuticals|Novartis||October 2017||Phase 2|
|NCT02939846||Withdrawn||Cancer||GlaxoSmithKline||May 2017||Phase 1|
|NCT02447939||Withdrawn||Melanoma||GlaxoSmithKline||May 2017||Phase 1|
|NCT02645149||Not yet recruiting||Melanoma||Melanoma Institute Australia||March 2017||Phase 4|
|NCT02967692||Not yet recruiting||Melanoma||Novartis Pharmaceuticals|Novartis||February 2017||Phase 3|
Could you help us with the best way to prepare Trametinib for in vivo i.p. injections?
S2673 can be dissovled in 4% DMSO/corn oil at 3 mg/ml clearly.
How to solve the problem that this product didn't dissolve up to 10mM in DMSO at room temperature?
The solution can be heated up to 50 degree to help dissolve. Besides, sonication (with a probe sonicator) also helped greatly.