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In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Trametinib (also known as GSK1120212 or JTP 74057), originally identified as a p15 inductive compound, is a novel and potent allosteric inhibitor of MEK kinase, which exhibits ATP non-competitive inhibition against MEK1 and MEK2 kinase. It has demonstrated broad antitumor activities in a variety of tumor xgenograft models, including HT-29 and COLO205 colorectal tumor cell lines. Trametinib induces expression of p15 and p27, reduces cyclin D1 levels, and causes dephosphorylation of RB protein and G1-phase arrest with a reduction of TS expression in HT-29 cells. It also effectively inhibits p-ERK 1/2 resulting in cell growth inhibition in tumor cell lines harboring B-RAF mutant.
Reference
Akintunde Akinleye, Muhammad Furqan, Nikhil Mukhi, Pavan Ravella and Delong Liu. MEK and the inhibitors: from bench to bedside. Journal of Hematology & Oncology 2013, 6:27
Motoki Watanabe, Yoshihiro Sowa, Mayumi Yogosawa and Toshiyuki Sakai. Novel MEK inhibitor trametinib and other retinoblastoma gene (RB)-reactivating agents enhance efficacy of 5-fluorouracil on human colon cancer cells. Cancer Sci 2013; 104(6): 687-693
Cell lines
HT-29 cells
Preparation method
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.
Reaction Conditions
100 nM, 72 hours
Applications
Trametinib showed a subnanomolar IC50 value for 72 h in a Cell Counting Kit-8 assay of human colon cancer HT-29 cells. The treatment with trametinib for 24 h dose-dependently increased the G1 phase with a decrease in the S phase, and 72 h treatment induced apoptosis in a dose-dependent manner together with G1 arrest.
Animal models
Male ICR mice
Dosage form
Oral administration, 3 mg/kg, daily
GSK1120212 was effective at blocking phosphorylation of ERK over 24 h and 7 d. To test whether the inhibitor blocked adaptive growth, mice were treated with GSK1120212 and/or the trypsin inhibitor camostat mesylate S (TI) for 7 d. TI-induced pancreatic growth was blocked by GSK1120212 as measured by pancreatic mass, protein, DNA, and RNA content. These results show that GSK1120212 like PD0325901 blocks pancreatic adaptive growth induced by TI.
Other notes
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References:
[1] Watanabe M, Sowa Y, Yogosawa M, et al. Novel MEK inhibitor trametinib and other retinoblastoma gene (RB)-reactivating agents enhance efficacy of 5‐fluorouracil on human colon cancer cells. Cancer science, 2013, 104(6): 687-693.
[2] Holtz B J, Lodewyk K B, Sebolt-Leopold J S, et al. ERK Activation is Required for CCK-mediated Pancreatic Adaptive Growth in Mice. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2014: ajpgi. 00163.2014.
