2. Academic Validation
  3. Identification of quinones as novel PIM1 kinase inhibitors

Identification of quinones as novel PIM1 kinase inhibitors

  • Bioorg Med Chem Lett. 2016 Jul 1;26(13):3187-3191. doi: 10.1016/j.bmcl.2016.04.079.
Richard L Schroeder 1,  Navneet Goyal 1,  Melyssa Bratton 2,  Ian Townley 2,  Nancy A Pham 1,  Phan Tram 1,  Treasure Stone 1,  Jasmine Geathers 1,  Kathy Nguyen 1,  Jayalakshmi Sridhar 3
Affiliations

Affiliations

  • 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.
PMID: 27173800 DOI: 10.1016/j.bmcl.2016.04.079
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.

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