Trametinib (Synonyms: GSK1120212; JTP-74057)

Name: Trametinib
Brand: MedChemExpress
SKU: HY-10999
Rating: 5.0 (203 reviews)

Cat. No.: HY-10999 Purity: 99.96%: FAQs
Data Sheet SDS COA Handling Instructions

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Trametinib (GSK1120212; JTP-74057) is an orally active MEK inhibitor that inhibits MEK1 and MEK2 with IC₅₀s of about 2 nM. Trametinib activates autophagy and induces apoptosis.

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

Trametinib Chemical Structure

CAS No. : 871700-17-3

Size	Price	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 66	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 66	In-stock	Estimated Time of Arrival: December 31
Solid
5 mg	USD 38	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 60	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 96	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 143	In-stock	Estimated Time of Arrival: December 31
500 mg	USD 430	In-stock	Estimated Time of Arrival: December 31
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5 g		Get quote

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Customer Review

Based on 203 publication(s) in Google Scholar

Other Forms of Trametinib:

186 Publications Citing Use of MCE Trametinib

: Trametinib purchased from MedChemExpress. Usage Cited in: Int J Cancer. 2019 Mar 15;144(6):1379-1390. [Abstract]; Western blot confirmed increased MAPK pathway activity in NEC-DUE2 cells when compared to NECDUE1. Treatment with PLX4032 (1 μM), GSK2118436A (100 nM), or Trametinib (100 nM) for 4 hours leads to decreased MAPK signaling in NEC-DUE2 cells. Lysates are immunoblotted for the proteins indicated.

: Trametinib purchased from MedChemExpress. Usage Cited in: Oncogenesis. 2019 Nov 4;8(11):65. [Abstract]; Western blot analysis of p-ERK and ERK protein levels in cell lysates of H1975 treated with AMPC, Trametinib for 24 h. The levels of the total ERK was used as an input control.

: Trametinib purchased from MedChemExpress. Usage Cited in: J Cell Sci. 2019 May 31;132(11):jcs224071. [Abstract]; Western blots of phosphorylated active ERK1/2 (pERK) and total ERK1/2 (ERK) for MDA MB 231 Sel2 and MDA MB 435 Sel1 populations following treatment with DMSO vehicle, 0.5 μM Trametinib or 10 μM U0126 for 18 h.

: Trametinib purchased from MedChemExpress. Usage Cited in: Cancer Discov. 2018 Mar;8(3):354-369. [Abstract]; MEK inhibitor Trametinib (GSK1120212) achieves target inhibition at 3mg/kg.

: Trametinib purchased from MedChemExpress. Usage Cited in: Sci Transl Med. 2018 Jul 18;10(450):eaaq1093. [Abstract]; Western blot analysis of selected MAPK and AKT/mTOR pathway components in Trametinib- and CCI-779-treated cells.

: Trametinib purchased from MedChemExpress. Usage Cited in: J Exp Clin Cancer Res. 2018 Sep 5;37(1):218. [Abstract]; WB for ERRα, IDH3A, c-Myc and Cyclin D1 in the HCT116 and SW480 cells treated with the indicated concentrations of Trametinib (0-100 nM) or DMSO for 48 h.

: Trametinib purchased from MedChemExpress. Usage Cited in: Proc Natl Acad Sci U S A. 2018 Oct 9;115(41):E9570-E9579. [Abstract]; presentative Western blots used to measure the efficiencies of kinase inhibitors in reducing ERK1/2 phosphorylation in control, ERK1/2 inhibitor (FR180204 and SCH772984; 10 μM)-treated or MEK1/2 inhibitor (GSK1120212; 10 μM)-treated ARPE-19 and H1299 cells.

: Trametinib purchased from MedChemExpress. Usage Cited in: Eur J Cancer. 2018 Aug;99:37-48. [Abstract]; Western blot detection of cleaved PARP in H358, SW480 and HCT-116 cell lines treated with BMS-354825 (100 nM), Trametinib (400 nM) or combination for 48 h. DMSO is used as the treatment control.

: Trametinib purchased from MedChemExpress. Usage Cited in: Biochem Biophys Res Commun. 2018 Jan 8;495(2):1846-1850. [Abstract]; 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 MedChemExpress. Usage Cited in: Patent. US20180161326A1.; Trametinib (100 nM) and PLX4032 (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 MedChemExpress. 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.

: Trametinib purchased from MedChemExpress. Usage Cited in: Sci Rep. 2017 Mar 28;7:45332. [Abstract]; Trametinib, a MEK1/2 inhibitor, strongly inhibits growth and partially reverses GW786034 resistance of GW786034-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 MedChemExpress. Usage Cited in: Oncotarget. 2017 Feb 28;8(9):14835-14846. [Abstract]; 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 MedChemExpress. Usage Cited in: Stem Cell Reports. 2016 Jan 12;6(1):74-84. [Abstract]; 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 MedChemExpress. Usage Cited in: Mol Cancer Ther. 2016 Aug;15(8):1859-69. [Abstract]; Addition of PAC-1 to the combination of PLX4032+Trametinib powerfully synergizes to induce apoptotic death and caspase activity in A375 and UACC-62 cells. Trametinib (100 nM) and PLX4032 (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 MedChemExpress. Usage Cited in: J Cell Biochem. 2016 Jun;117(6):1340-51. [Abstract]; 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 MedChemExpress. Usage Cited in: Cancer Discov. 2015 Sep;5(9):960-71. [Abstract]; The MEK inhibitor Trametinib effectively inhibits ERK phosphorylation at 30 nM in several EGFR mutant cell lines but has little effect on cell viability.

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Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

Trametinib (GSK1120212; JTP-74057) is an orally active MEK inhibitor that inhibits MEK1 and MEK2 with IC₅₀s of about 2 nM. Trametinib activates autophagy and induces apoptosis^[1]^[2].

IC₅₀ & Target^[1]

MEK1

2 nM (IC₅₀)

MEK2

2 nM (IC₅₀)

Cellular Effect

Cell Line	Type	Value	Description	References
A549	IC₅₀	0.46 μM Compound: 1	Antiproliferative activity against human A549 cells harboring KRAS G12S mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay Antiproliferative activity against human A549 cells harboring KRAS G12S mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay	[PMID: 32305784]
DLD-1	IC₅₀	1.34 μM Compound: 39	Anticancer activity against human DLD-1 cells assessed as reduction in cell viability incubated for 24 hrs by Cell Titer-Glo assay Anticancer activity against human DLD-1 cells assessed as reduction in cell viability incubated for 24 hrs by Cell Titer-Glo assay	[PMID: 33445154]
HCT-116	IC₅₀	0.019 μM Compound: 1	Antiproliferative activity against human HCT116 cells harboring KRAS G13D mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay Antiproliferative activity against human HCT116 cells harboring KRAS G13D mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay	[PMID: 32305784]
HCT-116	IC₅₀	1.16 μM Compound: 39	Anticancer activity against human HCT-116 cells assessed as reduction in cell viability incubated for 24 hrs by Cell Titer-Glo assay Anticancer activity against human HCT-116 cells assessed as reduction in cell viability incubated for 24 hrs by Cell Titer-Glo assay	[PMID: 33445154]
HL-60	IC₅₀	0.003 μM Compound: 1	Antiproliferative activity against human HL60 cells harboring NRAS K61L mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay Antiproliferative activity against human HL60 cells harboring NRAS K61L mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay	[PMID: 32305784]
MDA-MB-231	IC₅₀	0.018 μM Compound: 1	Antiproliferative activity against human MDA-MB-231 cells harboring KRAS G13D/BRAF G464V mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay Antiproliferative activity against human MDA-MB-231 cells harboring KRAS G13D/BRAF G464V mutant assessed as inhibition of cell viability after 96 hrs by Celltiter-Glo assay	[PMID: 32305784]
MDA-MB-231	GI₅₀	25 nM Compound: trametinib	Growth inhibition of human MDA-MB-231 cells after 3 days by DAPI staining Growth inhibition of human MDA-MB-231 cells after 3 days by DAPI staining	10.1039/C3MD00290J

In Vitro

Trametinib (GSK1120212;JTP-74057) (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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Adjuvant-induced arthritis (AIA) and type II collageninduced arthritis (CIA) development are suppressed almost completely by 0.1 mg/kg of Trametinib (GSK1120212; JTP-74057) or 10 mg/kg of HWA486^[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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

Molecular Weight

615.39

Formula

C₂₆H₂₃FIN₅O₄

CAS No.

871700-17-3

Appearance

Solid

Color

White to off-white

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

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

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

Solvent & Solubility

In Vitro:

DMSO : 25 mg/mL (40.62 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent 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

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (4.06 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (4.06 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 0.5% HPMC/1% Tween-80 in Saline water
Solubility: 6.67 mg/mL (10.84 mM); Suspended solution; Need ultrasonic

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Purity & Documentation

Purity: 99.96%

Select Batch:

Data Sheet (285 KB) SDS (393 KB)

COA (257 KB) RP-HPLC (242 KB) Elemental Analysis Report (114 KB)

Handling Instructions (2659 KB)

References

[1]. Yamaguchi T, et al. Suppressive effect of an orally active MEK1/2 inhibitor in two different animal models for rheumatoid arthritis: a comparison with HWA486. Inflamm Res, 2012, 61(5), 445-454. [Content Brief]

[2]. Yamaguchi T, et al. Antitumor activities of JTP-74057 (GSK1120212), a novel MEK1/2 inhibitor, on colorectal cancer cell lines in vitro and in vivo. Int J Oncol, 2011, 39(1), 23-31. [Content Brief]

[3]. Abe H, et al. Discovery of a Highly Potent and Selective MEK Inhibitor: GSK1120212 (JTP-74057 DMSO Solvate). ACS Med Chem Lett. 2011 Feb 28;2(4):320-4. [Content Brief]

[4]. Liu H, et al. Identifying and Targeting Sporadic Oncogenic Genetic Aberrations in Mouse Models of Triple Negative Breast Cancer. Cancer Discov. 2018 Mar;8(3):354-369. [Content Brief]

[5]. Lai J, et al. Elimination of melanoma by sortase A-generated TCR-like antibody-drug conjugates (TL-ADCs) targeting intracellular melanoma antigen MART-1. Biomaterials. 2018 Sep;178:158-169. [Content Brief]

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]	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]	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	[1]. Yamaguchi T, et al. Suppressive effect of an orally active MEK1/2 inhibitor in two different animal models for rheumatoid arthritis: a comparison with HWA486. Inflamm Res, 2012, 61(5), 445-454. [Content Brief] [2]. Yamaguchi T, et al. Antitumor activities of JTP-74057 (GSK1120212), a novel MEK1/2 inhibitor, on colorectal cancer cell lines in vitro and in vivo. Int J Oncol, 2011, 39(1), 23-31. [Content Brief] [3]. Abe H, et al. Discovery of a Highly Potent and Selective MEK Inhibitor: GSK1120212 (JTP-74057 DMSO Solvate). ACS Med Chem Lett. 2011 Feb 28;2(4):320-4. [Content Brief] [4]. Liu H, et al. Identifying and Targeting Sporadic Oncogenic Genetic Aberrations in Mouse Models of Triple Negative Breast Cancer. Cancer Discov. 2018 Mar;8(3):354-369. [Content Brief] [5]. Lai J, et al. Elimination of melanoma by sortase A-generated TCR-like antibody-drug conjugates (TL-ADCs) targeting intracellular melanoma antigen MART-1. Biomaterials. 2018 Sep;178:158-169. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	1.6250 mL	8.1249 mL	16.2499 mL	40.6246 mL
	5 mM	0.3250 mL	1.6250 mL	3.2500 mL	8.1249 mL
	10 mM	0.1625 mL	0.8125 mL	1.6250 mL	4.0625 mL
	15 mM	0.1083 mL	0.5417 mL	1.0833 mL	2.7083 mL
	20 mM	0.0812 mL	0.4062 mL	0.8125 mL	2.0312 mL
	25 mM	0.0650 mL	0.3250 mL	0.6500 mL	1.6250 mL
	30 mM	0.0542 mL	0.2708 mL	0.5417 mL	1.3542 mL
	40 mM	0.0406 mL	0.2031 mL	0.4062 mL	1.0156 mL

Trametinib Related Classifications

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Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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Trametinib (Synonyms: GSK1120212; JTP-74057)

Customer Review

Other Forms of Trametinib:

186 Publications Citing Use of MCE Trametinib

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References

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Complete Stock Solution Preparation Table

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Trametinib (Synonyms: GSK1120212; JTP-74057)

Customer Review

Other Forms of Trametinib:

Trametinib Related Antibodies

186 Publications Citing Use of MCE Trametinib

Featured Recommendations

•Related Screening Libraries:

•Related Small Molecules:

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View All MEK Isoform Specific Products:

Biological Activity

Protocol

Purity & Documentation

References

Customer Review

Trametinib Related Antibodies

Molarity Calculator

Dilution Calculator

Complete Stock Solution Preparation Table

Trametinib Related Classifications

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