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871700-17-3

871700-17-3 structure
871700-17-3 structure
  • Name: Trametinib (GSK1120212)
  • Chemical Name: trametinib
  • CAS Number: 871700-17-3
  • Molecular Formula: C26H23FIN5O4
  • Molecular Weight: 615.395
  • Catalog: Biochemical Inhibitor Mitogen-activated protein kinase (MAPK) MEK inhibitor
  • Create Date: 2018-04-13 08:00:00
  • Modify Date: 2024-01-02 14:15:26
  • Trametinib is a potent MEK inhibitor that inhibits MEK1 and MEK2 with IC50s of about 2 nM. Due to the poor solubility of Trametinib, Trametinib DMSO solvate (Cat. No.: HY-10999A) is recommeded.
Name trametinib
Synonyms UNII-33E86K87QN
GSK 1120212
GSK-1120212
Mekinist
N-(3-{3-Cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydropyrido[4,3-d]pyrimidin-1(2H)-yl}phenyl)acetamide
Acetamide, N-[3-[3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-3,4,6,7-tetrahydro-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl]-
GSK1120212
N-[3-[3-cyclopropyl-5-(2-fluoro-4-iodoanilino)-6,8-dimethyl-2,4,7-trioxopyrido[4,3-d]pyrimidin-1-yl]phenyl]acetamide
JTP74057
Trametinib
Description Trametinib is a potent MEK inhibitor that inhibits MEK1 and MEK2 with IC50s of about 2 nM. Due to the poor solubility of Trametinib, Trametinib DMSO solvate (Cat. No.: HY-10999A) is recommeded.
Related Catalog
Target

MEK1:2 nM (IC50)

MEK2:2 nM (IC50)

In Vitro Trametinib (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].
In Vivo Adjuvant-induced arthritis (AIA) and type II collageninduced arthritis (CIA) development are suppressed almost completely by 0.1 mg/kg of Trametinib (JTP-74057) or 10 mg/kg of Leflunomide[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].
Kinase Assay 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].
Cell Assay 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].
Animal Admin 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.
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 leflunomide. Inflamm Res, 2012, 61(5), 445-454.

[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.

[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.

[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.

[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.
Density 1.7±0.1 g/cm3
Molecular Formula C26H23FIN5O4
Molecular Weight 615.395
Exact Mass 615.077881
PSA 110.62000
LogP 2.68
Index of Refraction 1.734
Storage condition 2-8°C
Safety Phrases 24/25
HS Code 29339900

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title: CAS No. 871700-17-3 | Chemsrc address: https://www.chemsrc.com/en/baike/601341.html

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