Article
Discovery of MAP855, an Efficacious and Selective MEK1/2 Inhibitor with an ATP-Competitive Mode of Action.
Journal of medicinal chemistry - 10 Mar 2022
Poddutoori Ramulu, Aardalen Kimberly, Aithal Kiran, Barahagar Sanjeev Surendranath, Belliappa Charamanna, Bock Mark, Chelur Shekar, Gerken Andrea, Gopinath Sreevalsam, Gruenenfelder Bjoern, Kiffe Michael, Krishnaswami Maithreyi, Langowski John, Madapa Sudharshan, Narayanan Kishore, Pandit Chetan, Panigrahi Sunil Kumar, Perrone Mark, Potakamuri Ravi Kumar, Ramachandra Murali, Ramanathan Anuradha, Ramos Rita, Sager Emine, Samajdar Susanta, Subramanya Hosahalli S, Thimmasandra Devaraja Seethappa, Venetsanakos Eleni, Möbitz Henrik
Abstract excerpt
Mutations in MEK1/2 have been described as a resistance mechanism to BRAF/MEK inhibitor treatment. We report the discovery of a novel ATP-competitive MEK1/2 inhibitor with efficacy in wildtype (WT) and mutant MEK12 models. Starting from a HTS hit, we obtained selective, cellularly active compounds that showed equipotent inhibition of WT MEK1/2 and a panel of MEK1/2 mutant cell lines. Using a structure-based...
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