| Size | Price | Stock | Qty |
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| 25mg |
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| 500mg |
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Purity: ≥98%
Trametinib DMSO solvate, a potent MEK inhibitor with an IC50 value of about 2 nM, is the solvated form of trametinib (trametinib: dimethyl sulfoxide=1:1). Trametinib, also known as GSK1120212 or JTP 74057, has an IC50 of 0.92 nM/1.8 nM in cell-free assays and is a highly potent and specific MEK1/2 inhibitor. It has no effect on the kinase activities of c-Raf, B-Raf, or ERK1/2. Trametinib, which was initially thought to be a p15 inductive substance but was later discovered to be an allosteric inhibitor of MEK kinase, has the potential to have anti-cancer effects. Trametinib inhibits MEK1 and MEK2 kinase without competing for ATP. Trametinib binds to and specifically inhibits MEK 1 and 2, which prevents growth factor-mediated cell signaling and cellular proliferation in a variety of cancers. The RAS/RAF/MEK/ERK signaling pathway, which controls cell growth, is activated by the dual specificity threonine/tyrosine kinases MEK 1 and 2. These kinases are frequently upregulated in different cancer cell types. On May 29, 2013, the FDA granted Trametinib approval to treat melanoma.
| Targets |
MEK1 (IC50 = 2 nM); MEK2 (IC50 = 2 nM)
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| ln Vitro |
GSK1120212 has an IC50 range of 0.92 nM to 3.4 nM and inhibits the phosphorylation of MBP regardless of the isotypes of Raf and MEK. c-Raf, B-Raf, ERK1 and ERK2 are not inhibited by GSK1120212's kinase activity. Furthermore, the other 98 kinases are not significantly inhibited by GSK1120212 in a significant way. The human colorectal cancer cell lines are effectively inhibited by GSK1120212. The cells with the highest sensitivity to GSK1120212 have IC50 values of 0.48 nM and 0.52 nM, respectively, and are known to have a constitutively active B-Raf mutant in HT-29 and COLO205. The IC50 range for GSK1120212 in cell lines with a K-Ras mutation is 2.2–174 nM, indicating a wide range of sensitivity. In contrast, GSK1120212 is found to be resistant to COLO320 DM cells, which carry the wild-type gene in both B-Raf and K-Ras. This is true even at 10 μM. All sensitive cell lines undergo a 24-hour GSK1120212 treatment that results in cell-cycle arrest at the G1 phase. In most colorectal cancer cell lines, treatment with GSK1120212 causes an upregulation of p15INK4b and/or p27KIP1. In all vulnerable cell lines, GSK1120212 prevents constitutive ERK phosphorylation. Both HT-29 and COLO205 cells experience apoptosis induction from GSK1120212; however, COLO205 cells are more vulnerable to this induction than HT-29 cells.[1] GSK1120212 blocks tumor necrosis factor-α and interleukin-6 production from peripheral blood mononuclear cells (PBMCs).[2]
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| ln Vivo |
GSK1120212 can effectively stop the growth of the HT-29 xenograft when given orally at doses of 0.3 mg/kg or 1 mg/kg once daily for 14 days. At doses of 1 mg/kg, the tumor growth is almost entirely stopped. A single oral dose of 1 mg/kg GSK1120212 completely inhibits the phosphorylation of ERK1/2 in the tissues of established tumors, and after 14 days of treatment, the levels of the proteins p15INK4b and p27KIP1 are both increased. Tumor regression is seen in the COLO205 xenograft model even at a dose of 0.3 mg/kg. In 4 out of 6 mice receiving a dose of 1 mg/kg, the tumor completely regresses, resulting in tumor volume that cannot be measured.[1] Adjuvant-induced arthritis (AIA) and type II collagen-induced arthritis (CIA) in Lewis rats or DBA1/J mice, respectively, are almost completely suppressed by the administration of GSK1120212 at 0.1 mg/kg.[2]
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| Enzyme Assay |
Non-phosphorylated myelin basic protein (MBP) is coated onto an ELISA plate, and the active form of B-Raf/c-Raf is combined with unphosphorylated MEK1/MEK2, and ERERK2, in the presence of varying concentrations of GSK1120212. Using an anti-phospho-MBP antibody, MBP phosphorylation can be seen.
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| Cell Assay |
Exposure to GSK1120212 is followed by a 24-hour preculture of exponentially growing cells in 96-well tissue culture plates. An in vitro toxicology assay kit with sulforhodamine B as its main component measures cell growth. Both adherent and floating cells are gathered and fixed with 70% ethanol for use in the apoptosis assay. The cells are washed in PBS before being suspended in 100 g/mL RNase and 25 μg/mL propidium iodide (PI) and heated to 37 °C for 30 minutes in the dark. Using the flow cytometer Cytomics FC500 or Guava EasyCyte plus, the DNA content of each individual cell is identified.
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| Animal Protocol |
Mice: To create the A549 (human non-small cell lung carcinoma) model, tissue cultured cells are harvested aseptically and then digested with trypsin. Between 5×106 and 107 cells in 50% martigel are subcutaneously injected into female athymic mice (strain nu/nu). Before treatment, tumors are given one to four weeks to establish. The recommended doses of trametinib are given orally in amounts of 0.2 mL/20 g by weight. Vernier calipers are used every two weeks to measure tumors. When vehicle tumors reached a volume greater than 1000 mm3, antitumor activity was considered to be present. Tumor growth inhibition is defined as the percentage volume difference in tumor growth between the treated and control tumors at that time.
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| References |
| Molecular Formula |
C28H29FIN5O5S
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| Molecular Weight |
693.09
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| Exact Mass |
693.09182
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| Elemental Analysis |
C, 48.49; H, 4.21; F, 2.74; I, 18.30; N, 10.10; O, 11.53; S, 4.62
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| CAS # |
1187431-43-1
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| Related CAS # |
Trametinib;871700-17-3
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| Appearance |
Solid powder
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| 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.CS(=O)C
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| InChi Key |
OQUFJVRYDFIQBW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H23FIN5O4.C2H6OS/c1-13-22-21(23(31(3)24(13)35)30-20-10-7-15(28)11-19(20)27)25(36)33(17-8-9-17)26(37)32(22)18-6-4-5-16(12-18)29-14(2)34;1-4(2)3/h4-7,10-12,17,30H,8-9H2,1-3H3,(H,29,34);1-2H3
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| 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;methylsulfinylmethane
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.60 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (3.60 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (3.60 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4428 mL | 7.2141 mL | 14.4281 mL | |
| 5 mM | 0.2886 mL | 1.4428 mL | 2.8856 mL | |
| 10 mM | 0.1443 mL | 0.7214 mL | 1.4428 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01682083 | Completed | Drug: Dabrafenib Drug: Trametinib |
Melanoma | Novartis Pharmaceuticals | January 8, 2013 | Phase 3 |
| NCT02083354 | Completed | Drug: Dabrafenib Drug: Trametinib |
Cancer Melanoma |
Novartis Pharmaceuticals | March 18, 2014 | Phase 2 |
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