Trametinib (GSK1120212)

Trametinib (GSK1120212) is a highly specific and potent MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM, no inhibition of the kinase activities of c-Raf, B-Raf, ERK1/2. Phase 3.

Price Stock Quantity  
In DMSO USD 288 In stock
USD 120 In stock
USD 210 In stock
USD 670 In stock
USD 1070 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

Trametinib (GSK1120212) Chemical Structure

Trametinib (GSK1120212) Chemical Structure
Molecular Weight: 615.39

Validation & Quality Control

Customer Reviews(4)

Quality Control & MSDS

Related Compound Libraries

Trametinib (GSK1120212) is available in the following compound libraries:

MEK Inhibitors with Unique Features

Product Information

  • Inhibition Profile
  • Compare MEK Inhibitors
    Compare MEK Products
  • Research Area
  • Combination Therapy
    Combination Therapy

Product Description

Biological Activity

Description Trametinib (GSK1120212) is a highly specific and potent MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM, no inhibition of the kinase activities of c-Raf, B-Raf, ERK1/2. Phase 3.
Targets MEK1 MEK2
IC50 0.92 nM [1] 1.8 nM [1]
In vitro GSK1120212 inhibits the phosphorylation of MBP regardless of the isotype of Raf and MEK, with IC50 ranging from 0.92 nM to 3.4 nM. GSK1120212 demonstrates no inhibition of the kinase activities of c-Raf, B-Raf, ERK1 and ERK2. In addition, GSK1120212 does not show drastic inhibitory activity against the other 98 kinases. GSK1120212 displays potent inhibitory activity against human colorectal cancer cell lines. HT-29 and COLO205 cells, which are known to have a constitutively active B-Raf mutant, are most sensitive to GSK1120212 with IC50 0.48 nM and 0.52 nM, respectively. The cell lines bearing a K-Ras mutation show a wide range of sensitivity to GSK1120212 with IC50 of 2.2-174 nM. In contrast, COLO320 DM cells, bearing the wild-type gene in both B-Raf and K-Ras, are found to be resistant to GSK1120212 even at 10 μM. GSK1120212 treatment for 24 hours induces cell-cycle arrest at the G1 phase in all sensitive cell lines. Consistently, GSK1120212 treatment leads to upregulation of p15INK4b and/or p27KIP1 in most of the colorectal cancer cell lines. GSK1120212 inhibits constitutive ERK phosphorylation in all sensitive cell lines. GSK1120212 induces apoptosis both in HT-29 and COLO205 cells, but that COLO205 cells are more sensitive to GSK1120212 than HT-29 cells in terms of apoptosis induction. [1] GSK1120212 blocks tumor necrosis factor-α and interleukin-6 production from peripheral blood mononuclear cells (PBMCs). [2]
In vivo Oral administration of GSK1120212 at 0.3 mg/kg or 1 mg/kg once daily for 14 days is effective in inhibiting the HT-29 xenograft growth, and 1 mg/kg of GSK1120212 almost completely blocks the tumor increase. The phosphorylation of ERK1/2 is completely inhibited in the established tumor tissues by single oral dose of 1 mg/kg GSK1120212, and both p15INK4b and p27KIP1 protein levels are upregulated after 14 days of treatment with GSK1120212. In the COLO205 xenograft model, tumor regression is observed even at a dose of 0.3 mg/kg. At a dose of 1 mg/kg, a complete regression is obtained in 4 out of 6 mice in which the tumor degenerates to the point that tumor volume is not measurable. [1] Administration of GSK1120212 at 0.1 mg/kg almost completely suppresses adjuvant-induced arthritis (AIA) and type II collagen-induced arthritis (CIA) in Lewis rats or DBA1/J mice, respectively. [2]
Features More potent than PD0325901 or AZD6244.

Protocol(Only for Reference)

Kinase Assay: [1]

Raf-MEK-ERK cascade kinase assay Non-phosphorylated 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 ERERK2 in 10 μM ATP and 12.5 mM MgCl2 containing MOPS buffer in the presence of various concentrations of GSK1120212. The phosphorylation of MBP is detected by the anti-phospho-MBP antibody.

Cell Assay: [1]

Cell lines HT-29, HCT-15, HCT116, COLO205, LS-174T, SW480, SW620, T84, LoVo and COLO320
Concentrations Dissolved in DMSO, final concentrations ~10 μM
Incubation Time 3 or 4 days
Method Exponentially growing cells are precultured in 96-well tissue culture plates for 24 hours and then exposed to GSK1120212. Cell growth is determined by an in vitro toxicology assay kit, sulforhodamine B based. For apoptosis assay, both floating and adherent cells are collected and fixed with 70% ethanol. After washing with PBS, the cells are suspended in 100 μg/mL RNase and 25 μg/mL propidium iodide (PI) and incubated at 37 °C for 30 minutes in the dark. The DNA content of each single cell is determined using the flow cytometer Cytomics FC500 or Guava EasyCyte plus.

Animal Study: [1]

Animal Models Female BALB/c-nu/nu mice inoculated subcutaneously with HT-29 or COLO205 cells
Formulation Dissolved in 10% Cremophor EL-10% PEG400
Dosages ~1 mg/kg/day
Administration Orally
Solubility 30% PEG400/0.5% Tween80/5% propylene glycol, , 15 mg/mL
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
1

References

[1] Yamaguchi T, et al. Int J Oncol, 2011, 39(1), 23-31.

[2] Yamaguchi T, et al. Inflamm Res, 2012, 61(5), 445-454.

view more

Clinical Trial Information( data from http://clinicaltrials.gov)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02097225 Not yet recruiting Recurrent Melanoma|Stage IIIA Melanoma|Stage IIIB Melanoma|Stage IIIC Melanoma|Stage IV Melanoma National Cancer Institute (NCI) 2014-05 Phase 1
NCT02130466 Not yet recruiting Melanoma Merck Sharp & Dohme Corp.|Glaxo Wellcome 2014-05 Phase 1|Phase 2
NCT02138292 Not yet recruiting Melanoma University of Texas Southwestern Medical Center 2014-06 Phase 1
NCT02124772 Not yet recruiting Cancer GlaxoSmithKline 2014-07 Phase 1
NCT02093546 Not yet recruiting Endometrial Cancer M.D. Anderson Cancer Center|National Cancer Institute (NCI) 2014-09

Chemical Information

Download Trametinib (GSK1120212) SDF
Molecular Weight (MW) 615.39
Formula

C26H23FIN5O4

CAS No. 871700-17-3
Storage 3 years -20℃Powder
6 months-80℃in DMSO
Synonyms JTP-74057
Solubility (25°C) * In vitro DMSO 100 mg/mL heating (162 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 30% PEG400/0.5% Tween80/5% propylene glycol, 15 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name N-(3-(3-cyclopropyl-5-(2-fluoro-4-iodophenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl)phenyl)acetamide

Research Area

Customer Reviews (4)


Click to enlarge
Rating
Source one customer. Trametinib (GSK1120212) purchased from Selleck
Method Cell growth inhibition assay
Cell Lines Melanoma cell lines
Concentrations 0.00000256-5 μM
Incubation Time 72 h
Results GSK1120212 treatment inhibited Melanoma cells growth in a does-dependent manner.

Click to enlarge
Rating
Source J Neurosci,?012, 32(14), 4887-900.. Trametinib (GSK1120212) purchased from Selleck
Method Western blot
Cell Lines neurons
Concentrations 0.1 μM
Incubation Time
Results RDEA119 (1 μM) or JTP-74057 (0.1 μM) abolished the effects of G1 on the DAPK1 ( F (5, 24) 26.53, p < 0.01, Tukey’s test; p = 0.017, NMDA plus G1 plus RDEA vs NMDA plus G1; p < 0.01, NMDA plus G1 plus JTP vs NMDA plus G1) and NR2B phosphorylation (F(5, 24) 19.35, p < 0.01, Tukey’s test; p = 0.014, NMDA plus G1 plus RDEA vs NMDA plus G1; p = 0.046, NMDA plus G1 plus JTP vs NMDA plus G1.

Click to enlarge
Rating
Source Trametinib (GSK1120212) purchased from Selleck
Method Western blot analysis/ In vitro colony formation assay
Cell Lines LOX IMVI melanoma cells
Concentrations 0-1 μM
Incubation Time 24 h
Results As it is shown in Figure a, a strong induction of pErbB3, with concomitant increase of pAKT was observed 24 h after cell exposure to the MEK inhibitor. In vitro colony formation assays were run in the presence of growing concentrations of GSK1120212b alone or in combination with a fixed dose of A4. Also in this case, co-treatment with anti-ErbB3 strongly potentiated growth inhibition by the MEK inhibitor (Figure b). when cells were treated w ith suboptimal doses of vemurafenib and GSK1120212b, the addition of A4 was capable to provide a powerful synergis tic inhibition of cell growth (Figure c).

Click to enlarge
Rating
Source Jonas Nilsson, PhD from University of Gothenburg. Trametinib (GSK1120212) purchased from Selleck
Method Western blot, cell apoptosis assays
Cell Lines Mouse carcinoma cells
Concentrations 1-1000 nM
Incubation Time 16/40 h
Results (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=1-10 nM, GSK1120212=<1 nM.

Product Citations (16)

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related MEK Products

  • MEK162 (ARRY-162, ARRY-438162)

    ARRY-438162 is a potent inhibitor of MEK1/2 with IC50 of 12 nM.

  • Sorafenib

    Sorafenib is a multikinase inhibitor of Raf-1, B-Raf and VEGFR-2 with IC50 of 6 nM, 22 nM and 90 nM, respectively.

  • TAK-632

    TAK-632 is a potent pan-Raf inhibitor with IC50 of 8.3 nM and 1.4 nM for B-Raf(wt) and C-Raf, respectively, showing less or no inhibition against other tested kinases.

  • Selumetinib (AZD6244)

    Selumetinib (AZD6244) is a potent, highly selective MEK1 inhibitor with IC50 of 14 nM, also inhibits ERK1/2 phosphorylation with IC50 of 10 nM, no inhibition to p38α, MKK6, EGFR, ErbB2, ERK2, B-Raf, etc. Phase 1/2.

    Features:First MEK inhibitor being tested in Phase II clinical trials.

  • PD0325901

    PD0325901 (PD325901) is selective and non ATP-competitive MEK inhibitor with IC50 of 0.33 nM, roughly 500-fold more potent than CI-1040 on phosphorylation of ERK1 and ERK2. Phase 1/2.

  • U0126-EtOH

    U0126-EtOH is a highly selective inhibitor of MEK1/2 with IC50 of 0.07 μM/0.06 μM, 100-fold higher affinity for ΔN3-S218E/S222D MEK than PD098059.

    Features:A chemically synthesized and highly selective inhibitor of both MEK1 and MEK2.

  • PD98059

    PD98059 is a non-ATP competitive MEK inhibitor with IC50 of 2 μM, specifically inhibits MEK-1-mediated activation of MAPK; does not directly inhibit ERK1 or ERK2.

    Features:Does not inhibit c-Raf phosphorylated MEK1.

  • PD184352 (CI-1040)

    CI-1040 (PD 184352) is an ATP non-competitive MEK1/2 inhibitor with IC50 of 17 nM, 100-fold more selective for MEK1/2 than MEK5. Phase 2.

    Features:First MEK inhibitor to begin clinical development.

  • Pimasertib (AS-703026)

    AS-703026 is a highly selective, potent, ATP non-competitive allosteric inhibitor of MEK1/2 with IC50 of 5 nM-2 μM in MM cell lines. Phase 1/2.

    Features:A novel, highly selective and potent allosteric inhibitor of MEK1/2.

  • BIX 02189

    BIX02189 is a selective inhibitor of MEK5 with IC50 of 1.5 nM, also inhibits ERK5 catalytic activity with IC50 of 59 nM, and does not inhibit closely related kinases MEK1, MEK2, ERK2, and JNK2.

Recently Viewed Items

Tags: buy Trametinib (GSK1120212) | Trametinib (GSK1120212) supplier | purchase Trametinib (GSK1120212) | Trametinib (GSK1120212) cost | Trametinib (GSK1120212) manufacturer | order Trametinib (GSK1120212) | Trametinib (GSK1120212) distributor
Contact Us