Design and synthesis of novel allosteric MEK inhibitor CH4987655 as an orally available anticancer agent

…, S Tsujii, K Hattori, T Miura, Y Yoshimura, S Aida…

Index: Isshiki, Yoshiaki; Kohchi, Yasunori; Iikura, Hitoshi; Matsubara, Yasuaki; Asoh, Kohsuke; Murata, Takeshi; Kohchi, Masami; Mizuguchi, Eisaku; Tsujii, Shinji; Hattori, Kazuo; Miura, Takaaki; Yoshimura, Yasushi; Aida, Satoshi; Miwa, Masanori; Saitoh, Ryoichi; Murao, Naoaki; Okabe, Hisafumi; Belunis, Charles; Janson, Cheryl; Lukacs, Christine; Schueck, Verena; Shimma, Nobuo Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 6 p. 1795 - 1801

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Citation Number: 48

Abstract

The MAP kinase pathway is one of the most important pathways involved in cell proliferation and differentiation, and its components are promising targets for antitumor drugs. Design and synthesis of a novel MEK inhibitor, based on the 3D-structural information of the target enzyme, and then multidimensional optimization including metabolic stability, physicochemical properties and safety profiles were effectively performed and led to the ...