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Identification of quinones as novel PIM1 kinase inhibitors.

Abstract：

:PIM1 is a proto-oncogene encoding the serine/threonine PIM1 kinase. PIM1 kinase plays important roles in regulating aspects of cell cycle progression, apoptosis resistance, and has been implicated in the development of such malignancies as prostate cancer and acute myeloid leukemia among others. Knockout of PIM1 kinase in mice has been shown to be non-lethal without any obvious phenotypic changes, making it an attractive therapeutic target. Our investigation of anthraquinones as kinase inhibitors revealed a series of quinone analogs showing high selectivity for inhibition of the PIM kinases. Molecular modeling studies were used to identify key interactions and binding poses of these compounds within the PIM1 binding pocket. Compounds 1, 4, 7 and 9 inhibited the growth of DU-145 prostate cancer cell lines with a potency of 8.21μM, 4.06μM, 3.21μM and 2.02μM.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Schroeder RL,Goyal N,Bratton M,Townley I,Pham NA,Tram P,Stone T,Geathers J,Nguyen K,Sridhar J

doi

10.1016/j.bmcl.2016.04.079

subject

Has Abstract

pub_date

2016-07-01 00:00:00

pages

3187-3191

issue

13

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(16)30467-X

journal_volume

26

pub_type

杂志文章

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