Trametinib

Trametinib

Systematic (IUPAC) name
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
Clinical data
Trade names	Mekinist
Pregnancy category	US: D (Evidence of risk)
Legal status
Legal status	US: ℞-only
Identifiers
CAS Number	871700-17-3
ATC code	L01XE25 (WHO)
PubChem	CID 11707110
ChemSpider	9881833
UNII	33E86K87QN
ChEBI	CHEBI:75998
ChEMBL	CHEMBL2103875
Synonyms	GSK1120212
Chemical data
Formula	C26H23FIN5O4
Molar mass	615.39 g/mol
SMILES Ic1ccc(c(F)c1)N\C3=C\2/C(=O)N(C(=O)N(C/2=C(\C(=O)N3C)C)c4cccc(NC(=O)C)c4)C5CC5
InChI 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) Key:LIRYPHYGHXZJBZ-UHFFFAOYSA-N

Trametinib (trade name Mekinist) is a cancer drug. It is a MEK inhibitor drug with anti-cancer activity.^[1]

It inhibits MEK1 and MEK2.^[1]

Trametinib had good results for metastatic melanoma carrying the BRAF V600E mutation in a phase III clinical trial. In this mutation, the amino acid valine (V) at position 600 within the BRAF gene has become replaced by glutamic acid (E) making the mutant BRAF gene constitutively active.^[2]

In May 2013, trametinib was approved as a single-agent by the Food and Drug Administration for the treatment of patients with V600E mutated metastatic melanoma.^[3] Clinical trial data demonstrated that resistance to single-agent trametinib often occurs within 6 to 7 months.^[4] To overcome this, trametinib was combined with the BRAF inhibitor dabrafenib.^[4] As a result of this research, on January 8, 2014, the FDA approved the combination of dabrafenib and trametinib for the treatment of patients with BRAF V600E/K-mutant metastatic melanoma.^[5]

References

1. Trametinib, NCI Drug Dictionary
2. METRIC phase III study: Efficacy of trametinib (T), a potent and selective MEK inhibitor (MEKi), in progression-free survival (PFS) and overall survival (OS), compared with chemotherapy (C) in patients (pts) with BRAFV600E/K mutant advanced or metastatic melanoma (MM).
3. "GSK melanoma drugs add to tally of U.S. drug approvals". Reuters. May 30, 2013.
4. "Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations" 367 (18). New England Journal of Medicine. November 1, 2012: 1694–703. doi:10.1056/NEJMoa1210093. PMC 3549295. PMID 23020132.
5. "Dabrafenib/Trametinib Combination Approved for Advanced Melanoma". OncLive. January 9, 2014.