Design and synthesis of an in vivo-efficacious PIM3 kinase inhibitor as a candidate anti-pancreatic cancer agent

作者：Nakano Hirofumi; Hasegawa Tsukasa; Saito Nae; Furukawa Kaoru; Mukaida Naofumi; Kojima Hirotatsu; Okabe Takayoshi; Nagano Tetsuo^*

来源：Bioorganic & Medicinal Chemistry Letters, 2015, 25(24): 5687-5693.

DOI：10.1016/j.bmcl.2015.10.098

• PIM3
• Kinase inhibitor
• Drug design
• Anti-cancer agent
• Pancreatic cancer

Serine/threonine kinase PIM3 is a potential therapeutic target for pancreatic cancer. Here, we describe the evolution of our previous PIM1 inhibitor 1 into PIM3 inhibitor 11 guided by use of the crystal structure of PIM1 as a surrogate to provide a basis for rational modification. Compound 11 potently inhibits PIM3 kinase activity, as well as growth of several pancreatic cancer cell lines. In a mouse xenograft model, 11 inhibited growth of human pancreatic cancer cell line PCI66 with negligible body weight loss. Thus, 11 appears to be a promising lead compound for further optimization to develop new anti-pancreatic cancer agents.

• 出版日期2015-12-15