Title
Identification of Quinones as Novel PIM1 Kinase Inhibitors.
Funding Source
National Institute on Minority Health and Health Disparities, Louisiana Biomedical Research Network, U.S. Department of Defense
Grant Number
LBRN-P20GM103424, 2G12MD007595-06, W81XWH-11-1-0105
Department
Department of Chemistry
Document Type
Article
Publication Date
7-1-2016
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 8.21 μM, 4.06 μM, 3.21 μM and 2.02 μM.
Recommended Citation
Schroeder, R. L.; Goyal, Navneet; Bratton, M.; Townlee, I.; Pham, N; Tram, Phan; Stone, T.; Geathers, J; Nguyen, K; and Sridhar, Jayalakshmi, "Identification of Quinones as Novel PIM1 Kinase Inhibitors." (2016). Faculty and Staff Publications. 118.
https://digitalcommons.xula.edu/fac_pub/118
Comments
DOI: 10.1016/j.bmcl.2016.04.079
PubMed ID: 27173800
Funding text
This research work was funded by the NIH-RCMI ( 2G12MD007595-06 ) from the National Institute on Minority Health and Health Disparities , United States and the startup grant by the Louisiana Cancer Research Consortium . Additional support from the Department of Defense Award , United States ( W81XWH-11-1-0105 ), the Louisiana Biomedical Research Network ( LBRN-P20GM103424 ) is greatfully acknowledged. We thank the NIH-BUILD Grant—TL4MD009607 and the Center for Undergraduate Research at Xavier University of Louisiana for supporting the students who worked on this project. The contents are solely the responsibility of the authors and do not represent the official views of NIH, United States.