Home MAPK MEK inhibitor Trametinib (GSK1120212)

research use only

Trametinib (GSK1120212) MEK inhibitor

Cat.No.S2673

Trametinib (GSK1120212, JTP-74057) is a highly specific and potent MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM in cell-free assays, and it does not inhibit the kinase activities of c-Raf, B-Raf, ERK1/2. This compound activates autophagy and induces apoptosis.
Trametinib (GSK1120212) MEK inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 615.39

Jump to

Quality Control

Batch: Purity: 99.98%
99.98

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
MDA-MB-231, SW480 and SW1116 cells Function assay 100 nM 24 h trametinib could decrease YAP levels and inhibit LMB-induced YAP upregulation in MDA-MB-231, SW1116 and SW480 cells 30833665
RG7388-resistant U87MG cells Function assay 10 nM 24 h DMSO Trametinib treatment reduced the invasive phenotype of RG7388 resistant cells. 30274984
BJAB cells Function assay 0.01μM 24 h 0.01 μM trametinib effectively suppressed the ERK hyperactivation in BJAB cells caused by the combined treatment of BKM120 and Danusertib. 30947576
Human PDAC cell lines (MIA-PACA, PANC-1, CFPAC-1, PL45, CAPAN-2 and HPAF-II) Function assay 10 nM or 100 nM 3-days or 6-days The concentration of 10 nM trametinib consistently produced significant differences between gefitinib and trametinib alone compared to combination gefitinib and trametinib in all four sensitive cell lines (CFPAC-1, pl45, CAPAN-2 and HPAF-II). No additive effect was observed in the gefitinib insensitive or excitatory cell lines (MIA-Paca and PANC-1) 30921351
Transitional cell carcinoma (TCC) cell lines Function assay 25 nM 6-24 h Canine TCC cell lines are sensitive to MEK inhibition 31048548
COLO205 Growth inhibition assay 72 h IC50 = 0.001 μM ChEMBL
HT-29 Growth inhibition assay 72 h IC50 = 0.001 μM ChEMBL
COLO205 Growth inhibition assay 72 h IC50 = 0.001 μM ChEMBL
MV522 Growth inhibition assay 72 h IC50 = 0.001 μM ChEMBL
HT-29 Growth inhibition assay 72 h IC50 = 0.002 μM ChEMBL
MV522 Growth inhibition assay 72 h IC50 = 0.002 μM ChEMBL
NCI-H727 Growth inhibition assay 72 h IC50 = 0.002 μM ChEMBL
NCI-H727 Growth inhibition assay 72 h IC50 = 0.002 μM ChEMBL
SW1417 Growth inhibition assay 72 h IC50 = 0.003 μM ChEMBL
SW1417 Growth inhibition assay 72 h IC50 = 0.003 μM ChEMBL
Calu6 Growth inhibition assay 72 h IC50 = 0.003 μM ChEMBL
LS1034 Growth inhibition assay 72 h IC50 = 0.004 μM ChEMBL
SW1463 Growth inhibition assay 72 h IC50 = 0.004 μM ChEMBL
SW1463 Growth inhibition assay 72 h IC50 = 0.004 μM ChEMBL
Calu6 Growth inhibition assay 72 h IC50 = 0.004 μM ChEMBL
LS1034 Growth inhibition assay 72 h IC50 = 0.005 μM ChEMBL
RKO Growth inhibition assay 72 h IC50 = 0.005 μM ChEMBL
NCI-H508 Growth inhibition assay 72 h IC50 = 0.008 μM ChEMBL
KM12 Growth inhibition assay 72 h IC50 = 0.01 μM ChEMBL
A427 Growth inhibition assay 72 h IC50 = 0.01 μM ChEMBL
NCI-H1155 Growth inhibition assay 72 h IC50 = 0.01 μM ChEMBL
HCT8 Growth inhibition assay 72 h IC50 = 0.014 μM ChEMBL
MDA-MB-175-VII Growth inhibition assay 72 h IC50 = 0.016 μM ChEMBL
A549 Growth inhibition assay 72 h IC50 = 0.016 μM ChEMBL
RKO Growth inhibition assay 72 h IC50 = 0.018 μM ChEMBL
NCI-H23 Growth inhibition assay 72 h IC50 = 0.02 μM ChEMBL
A427 Growth inhibition assay 72 h IC50 = 0.022 μM ChEMBL
KM12 Growth inhibition assay 72 h IC50 = 0.023 μM ChEMBL
NCI-H508 Growth inhibition assay 72 h IC50 = 0.023 μM ChEMBL
MDA-MB-231 Growth inhibition assay 3 days GI50 = 0.025 μM ChEMBL
SW837 Growth inhibition assay 72 h IC50 = 0.025 μM ChEMBL
SW480 Growth inhibition assay 72 h IC50 = 0.026 μM ChEMBL
NCI-H1355 Growth inhibition assay 72 h IC50 = 0.027 μM ChEMBL
NCI-H23 Growth inhibition assay 72 h IC50 = 0.029 μM ChEMBL
EFM19 Growth inhibition assay 72 h IC50 = 0.03 μM ChEMBL
T84 Growth inhibition assay 72 h IC50 = 0.03 μM ChEMBL
A549 Growth inhibition assay 72 h IC50 = 0.034 μM ChEMBL
NCI-H1792 Growth inhibition assay 72 h IC50 = 0.035 μM ChEMBL
SW480 Growth inhibition assay 72 h IC50 = 0.037 μM ChEMBL
COR-L23 Growth inhibition assay 72 h IC50 = 0.037 μM ChEMBL
SW1573 Growth inhibition assay 72 h IC50 = 0.038 μM ChEMBL
Calu3 Growth inhibition assay 72 h IC50 = 0.039 μM ChEMBL
HCC827 Growth inhibition assay 72 h IC50 = 0.04 μM ChEMBL
HOP62 Growth inhibition assay 72 h IC50 = 0.05 μM ChEMBL
NCI-H1355 Growth inhibition assay 72 h IC50 = 0.052 μM ChEMBL
NCI-H1792 Growth inhibition assay 72 h IC50 = 0.053 μM ChEMBL
HCT8 Growth inhibition assay 72 h IC50 = 0.055 μM ChEMBL
T84 Growth inhibition assay 72 h IC50 = 0.061 μM ChEMBL
SW900 Growth inhibition assay 72 h IC50 = 0.072 μM ChEMBL
SW837 Growth inhibition assay 72 h IC50 = 0.074 μM ChEMBL
DLD1 Growth inhibition assay 72 h IC50 = 0.093 μM ChEMBL
MDA-MB-175-VII Growth inhibition assay 72 h IC50 = 0.096 μM ChEMBL
SW900 Growth inhibition assay 72 h IC50 = 0.127 μM ChEMBL
Calu3 Growth inhibition assay 72 h IC50 = 0.158 μM ChEMBL
COR-L23 Growth inhibition assay 72 h IC50 = 0.329 μM ChEMBL
DLD1 Growth inhibition assay 72 h IC50 = 0.632 μM ChEMBL
Click to View More Cell Line Experimental Data

Solubility

In vitro
Batch:

DMSO : 8 mg/mL (12.99 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight
Dilution Calculator Molecular Weight Calculator

In vivo
Batch:

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg
g
μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO
%
% Tween 80
% ddH2O
% DMSO
+
%

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight 615.39 Formula

C26H23FIN5O4

 Storage (From the date of receipt)
CAS No. 871700-17-3 Download SDF Storage of Stock Solutions

Synonyms JTP-74057 Smiles CC1=C2C(=C(N(C1=O)C)NC3=C(C=C(C=C3)I)F)C(=O)N(C(=O)N2C4=CC=CC(=C4)NC(=O)C)C5CC5

Mechanism of Action

Features
More potent than PD0325901 or AZD6244.
Targets/IC50/Ki
MEK1
(Cell-free assay)
0.92 nM
MEK2
(Cell-free assay)
1.8 nM
In vitro

Trametinib (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. It demonstrates no inhibition of the kinase activities of c-Raf, B-Raf, ERK1 and ERK2. In addition, this compound does not show drastic inhibitory activity against the other 98 kinases. It 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 it 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 it 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 even at 10 μM. Treatment for 24 hours induces cell-cycle arrest at the G1 phase in all sensitive cell lines. Consistently, it leads to upregulation of p15INK4b and/or p27KIP1 in most of the colorectal cancer cell lines. It inhibits constitutive ERK phosphorylation in all sensitive cell lines. This compound induces apoptosis both in HT-29 and COLO205 cells, but that COLO205 cells are more sensitive than HT-29 cells in terms of apoptosis induction. It blocks tumor necrosis factor-α and interleukin-6 production from peripheral blood mononuclear cells (PBMCs).

Kinase Assay
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 Trametinib (GSK1120212). The phosphorylation of MBP is detected by the anti-phospho-MBP antibody.
In vivo

Oral administration of Trametinib (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 this compound 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, and both p15INK4b and p27KIP1 protein levels are upregulated after 14 days of treatment. 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. Administration 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.

References
  • [4] https://pubmed.ncbi.nlm.nih.gov/22733540/

Applications

Methods Biomarkers Images PMID
Western blot ERRα / IDH3 / c-Myc / Cyclin D1 pERK /ERK / pS6 / S6 β-catenin
S2673-WB1
30185207
Growth inhibition assay Cell proliferation MTT assay
S2673-cell-proliferation1
30185207
Immunofluorescence phospho-PR(S345) β-catenin
S2673-IF1
29237804

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05275374 Not yet recruiting
Cancer|BRAF V600 Mutation|Melanoma|Colorectal Cancer|Thyroid Cancer|Nonsmall Cell Lung Cancer
Xynomic Pharmaceuticals Inc.
 December 2024 Phase 1|Phase 2
NCT06098872 Not yet recruiting
Arteriovenous Malformations
University Health Network Toronto
 November 2023 Phase 2
NCT05907304 Recruiting
Advanced or Metastatic Solid Tumors
Erasca Inc.
 August 17 2023 Phase 1
NCT05874414 Recruiting
Cholangiocarcinoma
Genfit
 August 21 2023 Phase 1|Phase 2

Tech Support

Handling Instructions

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

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

Frequently Asked Questions

Question 1:
Could you help us with the best way to prepare it for in vivo i.p. injections?

Answer:
It can be dissolved in 4% DMSO/corn oil at 3 mg/ml clearly.

Question 2:
How to solve the problem that it didn't dissolve up to 10mM in DMSO at room temperature?

Answer:
The solution can be heated up to 50 degrees to help dissolve it. Besides, sonication (with a probe sonicator) also greatly helps with this compound.

Signaling Pathway Map