GSK1120212 (DMSO solvate)

In May 2013, the US FDA approved trametinib (also referred to as GSK1120212 and JTP-74057), for the treatment of patients with unresectable or metastatic melanoma with BRAF^V600e or BRAF^V600K mutations as detected by an FDA-approved test. Extensive lead optimization led to the identification of trametinib which is a potent ATP noncompetitive inhibitor of MEK1 and MEK2 (IC₅₀ =0.7 and 0.9 nM, respectively, with initially unphosphorylated MEK). It also showed inhibitory activity in ACHN and HT-29 cancer cell lines (IC_50s of 9.8 and 0.57 nM, respectively). Consistent with its in vitro activity, trametinib showed significant antitumor activity in a KRAS^G12S A549 tumor xenograft model where near to complete tumor growth inhibition (TGI) was observed at 5.0 and 2.5 mg/kg (92% and 87% TGI, respectively). Broad antitumor activity was seen in other xenograft models as well. A synthetic route to trametinib that employs a base catalyzed rearrangement of a pyrido[2,3-d]pyrimidine core to pyrido[4,3-d]pyrimidine, as a key step has been reported.

Trametinib (DMSO Solvate) is a highly potent and selective MEK inhibitor with significant antitumor activity.

ChEBI: An addition compound obtained by combining equimolar amounts of trametinib and dimethyl sulfoxide. Used for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations, and who have not received prior BRAF inhibito treatment.