Home MAPK MEK inhibitor - Autophagy activator - Apoptosis related activator Trametinib DMSO solvate For research use only.

Trametinib DMSO solvate

Synonyms: GSK1120212, JTP-74057

Trametinib DMSO solvate is a highly specific and potent MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM in cell-free assay. Trametinib activates autophagy and induces apoptosis.

Trametinib DMSO solvate Chemical Structure

Trametinib DMSO solvate Chemical Structure

CAS: 1187431-43-1

Selleck's Trametinib DMSO solvate has been cited by 7 publications

Purity & Quality Control

Batch: Purity: 99.95%
99.95

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Biological Activity

Description Trametinib DMSO solvate is a highly specific and potent MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM in cell-free assay. Trametinib activates autophagy and induces apoptosis.
Targets
MEK1 [1]
(Cell-free assay)		 MEK2 [1]
(Cell-free assay)
0.92 nM 1.8 nM
In vitro
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]
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 GSK1120212. The phosphorylation of MBP is detected by the anti-phospho-MBP antibody.
Cell Research Cell lines HT-29, HCT-15, HCT116, COLO205, LS-174T, SW480, SW620, T84, LoVo and COLO320 cells
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.
In Vivo
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]
Animal Research Animal Models Female BALB/c-nu/nu mice inoculated subcutaneously with HT-29 or COLO205 cells
Dosages ~1 mg/kg/day
Administration o.g.
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 2023 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

Chemical lnformation & Solubility

Molecular Weight 693.53 Formula

C28H29FIN5O5S
CAS No. 1187431-43-1 SDF --
Smiles CN1C(=O)C(=C2N(C(=O)N(C3CC3)C(=O)C2=C1NC4=C(F)C=C(I)C=C4)C5=CC=CC(=C5)NC(C)=O)C.C[S](C)=O
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 6 mg/mL ( (8.65 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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