Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Trametinib (GSK1120212) is a MEK inhibitor that inhibits MEK1 and MEK2 (IC50=0.7/0.9 nM) with ATP non-competitive and oral activity. Trametinib activates autophagy and induces apoptosis.
Pack Size | Availability | Price/USD | Quantity |
---|---|---|---|
5 mg | In stock | $ 31.00 | |
10 mg | In stock | $ 50.00 | |
50 mg | In stock | $ 64.00 | |
100 mg | In stock | $ 100.00 | |
200 mg | In stock | $ 141.00 | |
1 mL * 10 mM (in DMSO) | In stock | $ 50.00 |
Description | Trametinib (GSK1120212) is a MEK inhibitor that inhibits MEK1 and MEK2 (IC50=0.7/0.9 nM) with ATP non-competitive and oral activity. Trametinib activates autophagy and induces apoptosis. |
Targets&IC50 | MEK2:0.92 nM (cell free), MEK1:1.8 nM (cell free) |
In vitro |
METHODS: Mouse intrahepatic cholangiocarcinoma cells SB1, LD-1 and human intrahepatic cholangiocarcinoma cells EGI-1 were treated with Trametinib (0-10,000 nM) for 48 h, and cell growth inhibition was detected by MTT. RESULTS: Trametinib dose-dependently inhibited the growth of SB1, LD-1 and EGI-1 cells with IC50 of 41.48 nM, 56.10 nM and 27.89 nM, respectively. [1] METHODS: Human colon cancer cells RKO were treated with Trametinib (200 nmol/L) for 30 h. The expression levels of target proteins were detected by Western Blot. RESULTS: Trametinib significantly reduced the levels of p-ERK and p-AKT. [2] METHODS: Human glioma cells U87 and U251 were incubated with Trametinib (50 nM) for 6-72 h. Apoptosis was detected by Flow Cytometry. RESULTS: Trametinib induced a significant increase in apoptosis in U87 and U251 cells, and Trametinib induced late apoptosis but not early apoptosis in glioma cells. [3] |
In vivo |
METHODS: To detect anti-tumor activity in vivo, Trametinib (0.3-1 mg/kg) was orally administered to BALB/c-nu/nu mice bearing human colorectal cancer tumors HT-29 and COLO205 once daily for fourteen days. RESULTS: Trametinib treatment significantly inhibited the growth of human colorectal cancer tumors, indicating antitumor activity in vivo. [4] METHODS: To assay antitumor activity in vivo, Trametinib (5 mg/kg) was injected intraperitoneally three times a week for fourteen days into NSG mice bearing human B-lymphoblastic leukemia tumors KOPN8 and COLO205. RESULTS: Trametinib monotherapy delayed the progression of leukemia, but was not sufficient to prevent leukemia growth. [5] |
Kinase Assay | A Raf-MEK-ERK cascade kinase assay was carried out as previously described. Briefly, nonphosphorylated myelin basic protein (MBP) was coated onto an ELISA plate, and the active form of B-Raf/c-Raf was mixed with unphosphorylated MEK1/MEK2 and ERK2 in 10 μM ATP and 12.5 mM MgCl2 containing MOPS buffer in the presence of various concentrations of JTP-74057. The phosphorylation of MBP was detected by the anti-phosphoMBP antibody. Kinase inhibitory activities against a total of 99 kinases were tested by kinase profiler at 10 μM ATP [1]. |
Cell Research | These cells were maintained in media recommended by the providers. Exponentially growing cells were precultured in 96-well tissue culture plates for 24 h and then exposed to JTP-74057. Cell growth was determined by an in vitro toxicology assay kit, sulforhodamine B based. For combination studies, two compounds were simultaneously added to the HT-29 cells and incubated for 72 h. In the presence of various concentrations of compound A, the 50% inhibitory concentration (IC50) values of compound B were determined. Then, the fixed concentration of compound A versus the IC50 value of compound B was plotted. Conversely, the IC50 values of compound A were determined in the presence of various concentrations of compound B and plotted [1]. |
Animal Research | Female BALB/c-nu/nu mice were used. On day 0, HT-29 cells or COLO205 cells suspended in ice-cold HBSS (-) were inoculated subcutaneously into the right flank of the mice at 5x10^6 cells/100 μl/site or 1x10^6 cells/100 μl/site, respectively. The acetic acid-solvated form of JTP-74057 was dissolved in 10% Cremophor EL-10% PEG400 and was administered orally once daily for 14 days from the day when the mean tumor volume reached 100 mm^3. The tumor length [L (mm)] and width [W (mm)] were measured using a micro gauge twice a week after the commencement of dosing, and the tumor volume was calculated using the following formula: tumor volume (mm^3) = L x W x W/2. All procedures relating to the use of animals in this study were reviewed and approved by the Institutional Animal Care and Use Committee of Japan Tobacco [1]. |
Synonyms | GSK1120212, JTP-74057 |
Molecular Weight | 615.39 |
Formula | C26H23FIN5O4 |
CAS No. | 871700-17-3 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 21 mg/mL (34.1 mM)
Ethanol: < 1 mg/mL (insoluble or slightly soluble)
You can also refer to dose conversion for different animals. More
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