Design and synthesis of novel allosteric MEK inhibitor CH4987655 as an orally available anticancer agent
Graphical abstract
Novel allosteric MEK inhibitor CH4987655 (24) possessing unique 3-oxo-[1,2]oxazinane substructure was designed and synthesized. CH4987655 shows slow dissociation from the target enzyme and high metabolic stability together with strong oral antitumor efficacy.
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Acknowledgments
We are grateful to N. Oikawa, H. Koyano, T. Hayase, S. Takeda, K. Morikami, K. Yoshinari, Y. Itezono, N. Nakayama, H. Shirai, H. Shindo, T. Mitsui, T. Ueto, R. Takano, N. Inagaki, Y. Inagaki, Y. Tomii, E. Hashimoto, R. Watanabe, K. Hamada, Y. Tachibana, N. Ishii, A. Kubota, H. Suzuki, T. Shiga, H. Matsumoto, T. Tsuno, A. Kawashima and all people who contributed to this project.
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