Mitogen-activated protein kinase kinase 1; Mitogen-activated protein kinase kinase 2 (MEK1 (for MAP2K1); MEK2 (for MAP2K2))

Mitogen-activated protein kinase kinase 1 (MEK1) and mitogen-activated protein kinase kinase 2 (MEK2) are **dual-specificity kinases** central to the MAPK/ERK pathway, responsible for phosphorylating and activating ERK1/2 and thus driving *cell proliferation, differentiation, apoptosis,* and *transcriptional regulation*. Their dysregulation is implicated in cancer development, progression, and resistance to therapy, making them highly validated targets for selective inhibition by small molecule drugs. Both MEK1 and MEK2 are activated by upstream RAF kinases and in turn activate the ERK subfamily, integrating diverse extracellular signals into precise cellular responses. Selective MEK inhibitors are used clinically, most notably in BRAF-mutated melanoma and increasingly in other solid tumors and hematologic cancers, with ongoing research into additional indications and combination regimens[2][4][5][6][7].

Other names

MAP2K1 (MEK1)MAP2K2 (MEK2)MEKMAPKKdual-specificity mitogen-activated protein kinase kinase

Inhibition of MEK1/2: Prevent phosphorylation and activation of downstream MAPKs (especially ERK1/2), blocking cell proliferation and inducing apoptosis in cancer cells. Allosteric inhibition: Some drugs bind sites distinct from the ATP-binding pocket, modulating kinase activity. MEK degradation: Certain novel compounds act as MEK degraders rather than pure inhibitors.