Name: Trametinib (GSK1120212)
Brand: GlpBio
SKU: GC13508
Availability: InStock
Rating: 5 (30 reviews)

GlpBio Products Cited In Reputable Papers

Nature
610.7931 (2022): 366-372

Nature
618, 1017–1023 (2023)

Cell
183.7 (2020): 1867-1883

Cell Research
31, 1291–1307 (2021)

Cell Research
33, 273–287 (2023)

Cell Research
33, 546–561 (2023)

Molecular Cancer
21.1 (2022): 1-17

Molecular Cancer
21.1 (2022): 1-18

Cancer Cell
39 (2021): 1-16

Cell Host Microbe
30.8 (2022): 1124-1138

Cell Host Microbe
31.5 (2023): 766-780

Cell Host Microbe
31.3 (2023): 418-43

Cell Metabolism
34.2 (2022): 240-255

Ann Rheum Dis
82(4): 533-545 (2023)

Cell Mol Immunol
20, 264–276 (2023)

Adv Funct Mater
33.35 (2023): 2214998

Product Documents

Quality Control & SDS

View current batch:

Purity: >99.00%

Protocol

Kinase experiment [1]:
Preparation Method	Two micrograms of dephosphorylated MBP (Upstate) in 0.2 M sodium carbonate (pH 9.4) was coated onto 96-well plates at 4 ¡ムovernight. After blocking with 1% BSA, the inactive forms of MEK1 (2 ng) or MEK2 (4 ng) with inactive ERK2 (50 ng) diluted in assay buffer were preincubated in the plates with test compounds£¨including Trametinib (GSK1120212)£©at room temperature for 10 min. The kinase reaction was started by the addition of active B-Raf (V599E) or c-Raf, with 10 M ATP and 12.5 mM MgCl2. After incubation at 30 C for 30 min, the phosphorylation of MBP by ERK2 was detected with peroxidase-labeled antiphosphorylated MBP antibody.
Reaction Conditions	Trametinib (GSK1120212) with protein at room temperature for 10 minutes
Applications	Trametinib (GSK1120212) binds specifically to MEK1/2.IC50 in cell-free assay was 0.92 nM/1.8 nM.
Cell experiment [1]:
Cell lines	HT-29 cells
Preparation Method	Cells were precultured for 24 h and then exposed to JTP-70902. After incubation with Trametinib (GSK1120212) for 4 days, cell viability was assessed using Cell Counting Kit-8.
Reaction Conditions	0-1000nM Trametinib (GSK1120212) for 4 days
Applications	Trametinib (GSK1120212), identified as a potent p15INKb inducer, modulates p27KIP1, cyclin D1, cyclin A and c-Myc protein levels and induces G1 arrest in HT-29 cells.
Animal experiment [1]:
Animal models	Trametinib (GSK1120212) in the nude mouse HT-29 xenograft model
Preparation Method	HT-29 cells were inoculated subcutaneously into the right flank of nude mice, and Trametinib (GSK1120212) was administered orally twice daily for 21 days starting from 5 days after the inoculation.
Dosage form	10-100mg/kg Trametinib (GSK1120212) twice daily for 21 days
Applications	Tumor growth was significantly suppressed in mice treated with 100 mg/kg Trametinib (GSK1120212) during the course of the treatment.
References: [1]. Yamaguchi T, Yoshida T,et,al. Identification of JTP-70902, a p15(INK4b)-inductive compound, as a novel MEK1/2 inhibitor. Cancer Sci. 2007 Nov;98(11):1809-16. doi: 10.1111/j.1349-7006.2007.00604.x. Epub 2007 Sep 2. PMID: 17784872.

Trametinib (GSK1120212, JTP-74057) is a second-generation small molecule inhibitor of MEK kinase. It functions as allosteric, ATP noncompetitive inhibitor with nanomolar activity against both MEK 1 and MEK 2 kinases with IC50 is 0.7-14.9 nM for MEK1/MEK2^[3,7].

Trametinib (GSK1120212), identified as a potent p15INKb inducer, modulates p27KIP1, cyclin D1, cyclin A and c-Myc protein levels and induces G1 arrest in HT-29 cells^[2]. Trametinib (GSK1120212) blocked tumor necrosis factor-α and interleukin-6 production from PBMCs. AIA and CIA development were suppressed almost completely by 0.1 mg/kg of JTP-74057 or 10 mg/kg of leflunomide. In the CIA, Trametinib (GSK1120212), but not leflunomide, suppressed collagen-reactive T-cell proliferation ex vivo^[1]. Among the different cell lines evaluated in the study, those with either BRAFV600E mutation or activating mutations in KRAS or NRAS were the most sensitive.Trametinib (GSK1120212) inhibited the MEK1/2-dependent activating dual phosphorylation of ERK1/2 on both T202 and Y204^[4].

In xenograft models of HT-29 and COLO205 colorectal tumor cell lines, trametinib demonstrated robust anticancer activity when administered daily for 14 days, Tumor growth was significantly suppressed in mice treated with 100 mg/kg Trametinib (GSK1120212) during the course of the treatment, by single oral dosing of 100 mg/kg Trametinib (GSK1120212), the phosphorylation of ERK1/2 in the established tumor tissues was completely inhibited, and both p15INK4b and p27KIP1 mRNA levels were upregulated in parallel^[2,5]. In patients treated with Trametinib (GSK1120212)for malignant melanoma most common adverse events observed were rash, diarrhea, peripheral edema, fatigue, and dermatitis acneiform^[6].

References:
[1]. Yamaguchi T, Kakefuda R, et,al. Suppressive effect of an orally active MEK1/2 inhibitor in two different animal models for rheumatoid arthritis: a comparison with leflunomide. Inflamm Res. 2012 May;61(5):445-54. doi: 10.1007/s00011-011-0431-5. Epub 2012 Jan 14. PMID: 22245957.
[2]. Yamaguchi T, Yoshida T, et,al. Identification of JTP-70902, a p15(INK4b)-inductive compound, as a novel MEK1/2 inhibitor. Cancer Sci. 2007 Nov;98(11):1809-16. doi: 10.1111/j.1349-7006.2007.00604.x. Epub 2007 Sep 2. PMID: 17784872.
[3]. be H, Kikuchi S, Hayakawa K, 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. doi: 10.1021/ml200004g. PMID: 24900312; PMCID: PMC4018163.
[4]. Gilmartin AG, Bleam MR, et,al. GSK1120212 (JTP-74057) is an inhibitor of MEK activity and activation with favorable pharmacokinetic properties for sustained in vivo pathway inhibition. Clin Cancer Res. 2011 Mar 1;17(5):989-1000. doi: 10.1158/1078-0432.CCR-10-2200. Epub 2011 Jan 18. Erratum in: Clin Cancer Res. 2012 Apr 15;18(8):2413. PMID: 21245089.
[5]. Gilmartin AG, Bleam MR, et,al. GSK1120212 (JTP-74057) is an inhibitor of MEK activity and activation with favorable pharmacokinetic properties for sustained in vivo pathway inhibition. Clin Cancer Res. 2011 Mar 1;17(5):989-1000. doi: 10.1158/1078-0432.CCR-10-2200. Epub 2011 Jan 18. Erratum in: Clin Cancer Res. 2012 Apr 15;18(8):2413. PMID: 21245089.
[6]. Flaherty KT, Infante JR, et,al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med. 2012 Nov 1;367(18):1694-703. doi: 10.1056/NEJMoa1210093. Epub 2012 Sep 29. PMID: 23020132; PMCID: PMC3549295.
[7]. Zeiser R, Andrlová H, et,al. Trametinib (GSK1120212). Recent Results Cancer Res. 2018;211:91-100. doi: 10.1007/978-3-319-91442-8_7. PMID: 30069762.

Cas No.	871700-17-3	SDF
Synonyms	GSK1120212, JTP-74057
Chemical Name	N-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]acetamide
Canonical 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
Formula	C₂₆H₂₃FIN₅O₄	M.Wt	615.39
Solubility	≥ 15.38mg/mL in DMSO	Storage	Store at -20°C
General tips	Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition	Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
		1 mg	5 mg	10 mg
	1 mM	1.625 mL	8.1249 mL	16.2499 mL
	5 mM	0.325 mL	1.625 mL	3.25 mL
	10 mM	0.1625 mL	0.8125 mL	1.625 mL

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In vivo Formulation Calculator (Clear solution)

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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.
3. All of the above co-solvents are available for purchase on the GlpBio website.

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Trametinib (GSK1120212) (Synonyms: GSK1120212, JTP-74057)

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