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Product Details:

  • Product Name: Trametinib
  • CAS #: 871700-17-3
  • Mode of Action:

    Trametinib is a reversible, allosteric inhibitor of mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2 activation and of MEK1 and MEK2 kinase activity. MEK proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway, which promotes cellular proliferation. Trametinib helps with melanoma with the BRAF V600E or V600K as the mutation results in the constitutive activation of the BRAF pathway which includes MEK1 and MEK2.

  • Pharmacodynamics:

    When 1 mg and 2 mg trametinib is given to patients with BRAF V600 mutation-positive melanoma, an inhibition of phosphorylated ERK and Ki67, and an increase in p27 was observed. These changes indicate that trametinib caused a decrease in cell proliferation and an increase in apoptosis, respectively.

  • Metabolism:

    Trametinib is metabolized predominantly via deacetylation alone or with mono-oxygenation or in combination with glucuronidation biotransformation pathways in vitro. Deacetylation is likely mediated by hydrolytic enzymes, such as carboxyl-esterases or amidases. The cytochrome P450 enzyme system is not involved with the metabolism of trametinib. The predominant circulating component in the plasma is the parent compound.

  • Toxicity:

    Most common adverse reactions (≥20%) for trametinib include rash, diarrhea, and lymphedema.

  • IUPAC: N-(3-{3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]-6, 8-dimethyl-2, 4, 7-trioxo-1H, 2H, 3H, 4H, 6H, 7H-pyrido[4, 3-d]pyrimidin-1-yl}phenyl)acetamide
  • ATC: L01XE25
  • Formula: C26H23FIN5O4
  • Molecular Mass: 615.3948
  • Synonyms: GSK 1120212, GSK1120212, JTP 74057, JTP-74057, 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, Trametinib, UNII-33E86K87QN
  • SMILES: CN1C(=O)C(C)=C2N(C(=O)N(C3CC3)C(=O)C2=C1NC1=CC=C(I)C=C1F)C1=CC(NC(C)=O)=CC=C1
  • AHFS Code: 10:00
  • InChl: InChI=1S/C26H23FIN5O4/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/h4-7,10-12,17,30H,8-9H2,1-3H3,(H,29,34)
  • General Reference:

    Salama AK, Kim KB: Trametinib (GSK1120212) in the treatment of melanoma. Expert Opin Pharmacother. 2013 Apr;14(5):619-27. doi: 10.1517/14656566.2013.770475. Epub 2013 Feb 23. Pubmed

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