Trametinib: A First in Class Oral MEK Inhibitor Approved for Treatment of Metastatic Melanoma With BRAF V600 Mutations

Randa Hilal-Dandan, PhD


AccessMedicine from McGraw-Hill 

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Trametinib (MEKINIST; Figure 1) is a first-in-class, orally administered selective inhibitor of MEK1/2 serine-threonine kinase. In late May 2013, the FDA approved trametinib for the treatment of patients with unresectable or metastatic melanoma harboring activating BRAF V600E/K mutations.[1,2] The FDA also approved a companion diagnostic kit THxID-BRAF, to confirm BRAF V600E/K mutations.[1] Trametinib in monotherapy was shown to significantly improve progression-free survival (PFS) in patients with BRAF V600E/K melanoma and extend overall survival compared to patients on standard therapy.[1,2,3] Trametinib is not indicated for patients that have received prior BRAF inhibitor therapy. Promising clinical data suggest that combination therapy of trametinib and the BRAF inhibitor dabrafenib in patients with BRAF V600E/K melanoma is additive and will improve PSF compared to monotherapy with either drug alone.[4]

Figure 1.

Chemical Structure of Trametinib (GSK1120212). Chemical name: 5-(2-(5,6-diethylindan-2-ylamino)-1-hydroxyethyl)-8-hydroxy-1H-quinolin-2-one - PubChem Compound ID: 11707110