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

Abstract：

: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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Nakano H,Hasegawa T,Saito N,Furukawa K,Mukaida N,Kojima H,Okabe T,Nagano T

doi

10.1016/j.bmcl.2015.10.098

subject

Has Abstract

pub_date

2015-12-15 00:00:00

pages

5687-93

issue

24

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(15)30208-0

journal_volume

25

pub_type

杂志文章

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