1. MAPK/ERK Pathway
  2. MEK

Trametinib (Synonyms: GSK1120212; JTP-74057)

Cat. No.: HY-10999 Purity: 99.37%
Handling Instructions

Trametinib is a potent MEK inhibitor that specifically inhibits MEK1/2, with an IC50 value of about 2 nM. Due to the poor solubility of Trametinib, Trametinib DMSO solvate (Cat. No.: HY-10999A) is the more commonly used form.

For research use only. We do not sell to patients.

Trametinib Chemical Structure

Trametinib Chemical Structure

CAS No. : 871700-17-3

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10 mM * 1 mL in DMSO USD 66 In-stock
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Estimated Time of Arrival: December 31
50 mg USD 96 In-stock
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100 mg USD 143 In-stock
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Customer Review

Other Forms of Trametinib:

    Trametinib purchased from MCE. Usage Cited in: Stem Cell Reports. 2016 Jan 12;6(1):74-84.

    Western blot of SKPs treated with varying concentrations of Trametinib (MEKi) or DMSO (Control) for 30 min, probed for pERK1/2 and reprobed for total ERK1/2.

    Trametinib purchased from MCE. Usage Cited in: Cancer Discov. 2015 Sep;5(9):960-71.

    The MEK inhibitor Trametinib effectively inhibits ERK phosphorylation at 30 nM in several EGFR mutant cell lines but has little effect on cell viability.

    Trametinib purchased from MCE. Usage Cited in: Cancer Discov. 2018 Mar;8(3):354-369.

    In vivo dosing of BGJ398 at 30mg/kg achieves target inhibition measured by pFrs2 and pErk levels.

    Trametinib purchased from MCE. Usage Cited in: Biochem Biophys Res Commun. 2018 Jan 8;495(2):1846-1850.

    Western blot analysis of phosphorylated ERK2, and ERK2 in microvesicle-depleted fraction (15 μg of protein) derived from viruses obtained from 10 nM Trametinib-treated CEM/LAV-1 cells.

    Trametinib purchased from MCE. Usage Cited in: Cancer Discov. 2018 Mar;8(3):354-369.

    MEK inhibitor Trametinib (GSK1120212) achieves target inhibition at 3mg/kg.

    Trametinib purchased from MCE. Usage Cited in: Oncotarget. 2015 Oct 13;6(31):31313-22.

    Effect of Ibrutinib on EGFR wt/mutant NSCLCs. Ibrutinib effects on wt EGFR and mutant EGFR- mediated signaling pathways. The results demonstrate that Ibrutinib potently inhibits both EGFR wt/mutant auto-phosphorylation at Y1068.

    Trametinib purchased from MCE. Usage Cited in: Oncotarget. 2015 Oct 13;6(31):31313-22.

    Effect of Ibrutinib, WZ4002, AZD9291 and CO1686 on EGFR phosphorylation of tyrosines 1068 and 1173 in EGFR-dependent cancer cell lines.

    Trametinib purchased from MCE. Usage Cited in: Cancer Discov. 2018 Mar;8(3):354-369.

    At 50mg/kg, Crizotinib inhibits MET phosphorylation and downstream signaling pathway activation.

    Trametinib purchased from MCE. Usage Cited in: J Cell Biochem. 2016 Jun;117(6):1340-51.

    HeLa S3 cells that are arrested at the G2/M border by RO-3306 treatment are washed free of RO-3306 and incubated with 10 μM GSK1120212.

    Trametinib purchased from MCE. Usage Cited in: Mol Cancer Ther. 2016 Aug;15(8):1859-69.

    Addition of PAC-1 to the combination of Vemurafenib+Trametinib powerfully synergizes to induce apoptotic death and caspase activity in A375 and UACC-62 cells. Trametinib (100 nM) and Vemurafenib (10 μM) in combination have little effect on PARP-1 cleavage in A375 and UACC-62 cells, but significant PARP-1 cleavage and reduction in procaspase-3 level are observed via Western blot with the addition of PAC-1 (12 μM).

    Trametinib purchased from MCE. Usage Cited in: Oncotarget. 2017 Feb 28;8(9):14835-14846.

    MEK inhibition results in reduced ERK phosphorylation.A. Western blot analysis of SEM and KOPN8 exposed to 500 nM of MEK inhibitor or vehicle control (DMSO) for 6, 24 and 48 hours. Both cell lines almost completely lose ERK phosphorylation (p-ERK), while total ERK (t-ERK) levels remain unaffected. B. Analysis of MEK phosphorylation (p-MEK) suggests exposure to MEK162 and Selumetinib results in enhanced MEK phosphorylation in both cell lines, whereas total MEK (t-MEK) levels remain constant.

    Trametinib purchased from MCE. Usage Cited in: Cancer Lett. 2017 Aug 18;408:43-54.

    Western blot analysis of p-ERK, ERK, p-AKT and ERK after 24 h of treatment with Vemurafenib. Levels of p-ERK and p-AKT are quantified by densitometric analysis and a corresponding histogram is constructed as relative to ERK or AKT and α-tubulin. Representative Western blot panels on the left.

    Trametinib purchased from MCE. Usage Cited in: Cancer Lett. 2017 Aug 18;408:43-54.

    Western blot analysis of p-p70S6k, p70S6k, p-AKT and AKT after 6 h of treatment with 20 μM Everolimus. Levels of p-p70S6k and p-AKT are quantified by densitometric analysis and a corresponding histogram is constructed as relative to p70S6k or AKT and α-tubulin. The lower panel shows a representative Western blot.

    Trametinib purchased from MCE. Usage Cited in: Sci Rep. 2017 Mar 28;7:45332.

    Trametinib, a MEK1/2 inhibitor, strongly inhibits growth and partially reverses Pazopanib resistance of Pazopanib-resistant clones.Trametinib-induced inhibition of phosphorylation of ERK1/2 in SS clones is assessed by Western blot analysis with anti-ERK1/2 and anti-phospho-ERK1/2 antibodies. SS clones are pre-treated using 10 nMtrametinib for 2 hours.

    Trametinib purchased from MCE. Usage Cited in: Cell Chem Biol. 2018 May 18. pii: S2451-9456(18)30155-7.

    Negligible increases in caspase-3 activity or PARP-1 cleavage is observed in H1975 NSCLC cells treated with DMSO, single agent PAC-1 (5 mM), or Osimertinib (Osi). In cells treated with PAC-1+Osimertinib, dramatic increases in caspase-3 activity is observed as early as 36 hr post treatment.

    Trametinib purchased from MCE. Usage Cited in: Cell Chem Biol. 2018 May 18. pii: S2451-9456(18)30155-7.

    Negligible increases in caspase-3 activity or PARP-1 cleavage is observed in PC-9 GR NSCLC cells treated with DMSO, single agent PAC-1 (5 mM), or Osimertinib (Osi). In cells treated with PAC-1+Osimertinib, dramatic increases in caspase-3 activity is observed as early as 36 hr post treatment.

    Trametinib purchased from MCE. Usage Cited in: bioRxiv. June 13, 2018.

    Representative western blots used to measure the efficiencies of kinase inhibitors in reducing ERK1/2 phosphorylation in control, FR180204 10 μM and SCH772984, 10 μM and GSK1120212, 10 μM treated ARPE-19 and H1299 cells.

    Trametinib purchased from MCE. Usage Cited in: Patent. US20180161326A1.

    Trametinib (100 nM) and Vemurafenib (10 μM) in combination have little effect on PARP-1 cleavage in A375 and UACC-62 cells, but significant PARP-1 cleavage and reduction in procaspase-3 level are observed via Western blot with the addition of PAC-1 (12 μM).

    Trametinib purchased from MCE. Usage Cited in: Clin Cancer Res. 2014 Nov 1;20(21):5483-95.

    Effects of GSK1904529A and AZD6244 as single agents, respectively, on mediators of IGF-1R- and ERK1/ERK2-signaling pathways.(A–B) Effect of GSK1904529A on phosphorylation of IGF-1R (A) and Erk1/Erk2 (B). (C–E) Effect of AZD6244 on phosphorylation of IGF-1R (C), IGF-1R protein expression levels (D), and phosphorylation of Erk1/Erk2 (E). GSK1904529A is observed to inhibit phosphorylation of IGF-1R in a concentration-dependent manner (A), however shows no inhibitory activity against phosphorylation

    Trametinib purchased from MCE. Usage Cited in: Eur J Cancer. 2018 Aug;99:37-48.

    Western blot detection of cleaved PARP in H358, SW480 and HCT-116 cell lines treated with Dasatinib (100 nM), Trametinib (400 nM) or combination for 48 h. DMSO is used as the treatment control.

    Trametinib purchased from MCE. Usage Cited in: Patent. US20180169102A1.

    The presence or absence of the pERK protein are measured through western blotting using the brain hemispheres of trametinib-administered 5×FAD mice.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    Trametinib is a potent MEK inhibitor that specifically inhibits MEK1/2, with an IC50 value of about 2 nM. Due to the poor solubility of Trametinib, Trametinib DMSO solvate (Cat. No.: HY-10999A) is the more commonly used form.

    IC50 & Target

    IC50: 2 nM (MEK1/2)[1]

    In Vitro

    Trametinib (0.1-100 nM) blocks tumor necrosis factor-α and interleukin-6 production from peripheral blood mononuclear cells (PBMCs). Trametinib (JTP-74057) inhibits the growth of 9 out of 10 human colorectal cancer cell lines, and they shows cell-cycle arrest at the G1 phase after drug tratment[1]. The combination of GSK2118436 and Trametinib (GSK1120212) effectively inhibits cell growth, decreases ERK phosphorylation, decreases cyclin D1 protein, and increases p27(kip1) protein in the resistant clones[2].

    In Vivo

    Adjuvant-induced arthritis (AIA) and type II collageninduced arthritis (CIA) development are suppressed almost completely by 0.1 mg/kg of Trametinib (JTP-74057) or 10 mg/kg of Leflunomide[1]. Trametinib (0.3 mg/kg, 1 mg/kg, p.o.) is effective in inhibiting the HT-29 xenograft growth in a nude mouse xenograft model[2].

    Clinical Trial
    References
    Preparing Stock Solutions
    Concentration Volume Mass 1 mg 5 mg 10 mg
    1 mM 1.6250 mL 8.1249 mL 16.2499 mL
    5 mM 0.3250 mL 1.6250 mL 3.2500 mL
    10 mM 0.1625 mL 0.8125 mL 1.6250 mL
    Please refer to the solubility information to select the appropriate solvent.
    Kinase Assay
    [2]

    The nonphosphorylated myelin basic protein (MBP) is coated onto an ELISA plate, and the active form of B-Raf/c-Raf is 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 Trametinib (JTP-74057). The phosphorylation of MBP is detected by the anti-phosphoMBP antibody. Kinase inhibitory activities against a total of 99 kinases are tested at 10 µM ATP[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Cell Assay
    [2]

    Heating Trametinib at 80°C in DMSO for 10 min-30 min to get a clear solution and then cool to room temperature[3].

    Cells are treated with various concentrations of Trametinib (JTP-74057) in 100 mm dishes for 3 or 4 days. Both floating and adherent cells are collected and fixed with 70% ethanol. After washing with PBS, the cells are suspended in 100 µL/mL RNase and 25 µL/mL Propidium iodide (PI) and incubated at 37°C for 30 min in the dark. The DNA content of each single cell is determined using the flow cytometer Cytomics FC500 or Guava EasyCyte plus[2].
    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [2]

    Trametinib is dissolved in 10% Cremophor EL-10% PEG400 (Mice)[2].

    Mice[2]
    Female BALB/c-nu/nu mice are used. On day 0, HT-29 cells or COLO205 cells suspended in ice-cold HBSS (-) are inoculated subcutaneously into the right flank of the mice at 5×106 cells/100 µL/site or 1×106 cells/100 µL/site, respectively. The acetic acid-solvated form of Trametinib (JTP-74057, 0.3 mg/kg, 1 mg/kg) is dissolved in 10% Cremophor EL-10% PEG400 and is administered orally once daily for 14 days from the day when the mean tumor volume reached 100 mm3. The tumor length [L(mm)] and width [W(mm)] are measured using a microgauge twice a week after commencement of dosing, and the tumor volume is calculated using the following formula: tumor volume (mm3)=L×W×W/2. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    615.39

    Formula

    C₂₆H₂₃FIN₅O₄

    CAS No.

    871700-17-3

    SMILES

    CC(NC1=CC=CC(N(C2=O)C(C(C(N2C3CC3)=O)=C(N4C)NC5=CC=C(C=C5F)I)=C(C4=O)C)=C1)=O

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Solvent & Solubility

    DMSO: ≥ 69 mg/mL (Heating Trametinib at 80°C in DMSO for 10 min-30 min to get a clear solution and then cool to room temperature)[3]

    Trametinib (GSK1120212) is prepared in vehicle (10% Cremophor EL/10% PEG400)[4].
    Trametinib is dissolved in 0.5% hydroxypropyl methylcellulose with 0.2% Tween 80[5].

    * "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

    References

    Purity: 99.37%

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    Product Name:
    Trametinib
    Cat. No.:
    HY-10999
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