Rational evolution of a novel type of potent and selective proviral integration site in Moloney murine leukemia virus kinase 1 (PIM1) inhibitor from a screening-hit …

…, K Tsuganezawa, S Yokoyama, A Tanaka…

Index: Nakano, Hirofumi; Saito, Nae; Parker, Lorien; Tada, Yukio; Abe, Masanao; Tsuganezawa, Keiko; Yokoyama, Shigeyuki; Tanaka, Akiko; Kojima, Hirotatsu; Okabe, Takayoshi; Nagano, Tetsuo Journal of Medicinal Chemistry, 2012 , vol. 55, # 11 p. 5151 - 5164

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Citation Number: 25

Abstract

Serine/threonine kinase PIM1 is an emerging therapeutic target for hematopoietic and prostate cancer therapy. To develop a novel PIM1 inhibitor, we focused on 1, a metabolically labile, nonselective kinase inhibitor discovered in our previous screening study. We adopted a rational optimization strategy based mainly on structural information for the PIM1-1 complex to improve the potency and selectivity. This approach afforded the potent and ...