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Bioorg Med Chem Lett. 2016 Jul 1;26(13):3187-3191. doi: 10.1016/j.bmcl.2016.04.079. Epub 2016 Apr 28.

Identification of quinones as novel PIM1 kinase inhibitors.

Author information

1
Department of Chemistry, Xavier University of Louisiana, 1, Drexel Dr., New Orleans, LA 70125, USA.
2
Cell and Molecular Biology Core Facility, Xavier University of Louisiana, New Orleans, LA 70125, USA.
3
Department of Chemistry, Xavier University of Louisiana, 1, Drexel Dr., New Orleans, LA 70125, USA. Electronic address: jsridhar@xula.edu.

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.

KEYWORDS:

Emodin; Pim1 kinase; Prostate cancer; Quinones; Selectivity profile

PMID:
27173800
PMCID:
PMC4899092
DOI:
10.1016/j.bmcl.2016.04.079
[Indexed for MEDLINE]
Free PMC Article

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