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Identifier: R-HSA-9657603
Species: Homo sapiens
Compartment: plasma membrane, cytosol
A number of 'dual mechanism' MAPK inhibitors are in preclinical or clinical trials (reviewed in Roskoski, 2019). Dual mechanism inhibitors, including the ATP-competitive inhibitors SCH772984 and MK-8353, bind to the unphosphorylated MAPK and prevent both its own kinase activity and its phosphorylation by MAP2Ks (Morris et al, 2013; Deng et al 2014; Chaikuad et al, 2014; Boga et al, 2018; Moschos et al, 2019; reviewed in Samatar and Poulikakos, 2014). MAPK inhibitors offer the potential to mitigate the development of resistance to RAF and MAP2K inhibitors, which often involves reactivation of MAPK-dependent signaling. As a result, MAPK inhibitors are frequently used in combination with RAF and MAP2K-directed therapeutics (reviewed in Samatar and Poulikakos, 2014; Roskoski, 2019).
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