Trametinib is identified as a reversible and remarkably selective allosteric inhibitor of MEK1 and MEK2. Through its high-affinity binding to unphosphorylated MEK1 and MEK2, trametinib effectively impedes the catalytic activity of these enzymes. Moreover, it plays a crucial role in preserving MEK in an unphosphorylated state, consequently impeding the phosphorylation and subsequent activation of MEKs.
In the context of adjuvant therapy, trametinib is utilized in combination with dabrafenib following the complete surgical removal of melanoma that involves nodal involvement and carries either the BRAF V600E or V600K mutation
Trametinib, when combined with dabrafenib, is employed as a treatment strategy for metastatic non-small cell lung cancer (NSCLC) in patients with the BRAF V600E mutation. This specific combination has been designated as an orphan drug by the FDA for this particular application.
Anaplastic Thyroid Cancer
Trametinib, in conjunction with dabrafenib, is utilized as a treatment approach for locally advanced or metastatic anaplastic thyroid cancer in patients with the BRAF V600E mutation when other satisfactory locoregional treatment options are not available. The FDA has designated this particular combination as an orphan drug for this specific therapeutic application.