Accession Number:

AD1016350

Title:

A Computational Framework for Design and Development of Novel Prostate Cancer Therapies

Descriptive Note:

Technical Report,01 Sep 2014,31 Aug 2015

Corporate Author:

University of California, Davis Davis United States

Personal Author(s):

• Bhardwaj,Gaurav

Report Date:

2015-09-01

Pagination or Media Count:

27.0

Abstract:

Tek protein kinases, such as Etk and Btk, play key roles in the survival and proliferation ofprostate cancer cells. We developed novel computational and combinatorial frameworks fordesign and development of small molecule inhibitors targeting Etk. Large scale in silicoscreening of virtual libraries was used to identify novel Etk inhibitors. Experimentalstudies with small-molecule ligands identified from computational screens show promising cellgrowth inhibition for PC3 cells in cell culture based experiments. In addition, we usedphylogenetic and structural studies to identify novel target sites. Overall, thecomputational methods developed here can be used to rapidly scan and develop potent enzymeinhibitors, and more generally provide drug leads for late-stage prostate cancer.

Descriptors:

• epithelial cells
• gene expression
• cell physiological processes
• prostate cancer
• therapeutics
• peptides
• neoplasms
• carcinoma
• proteins
• tissues biology
• therapeutics
• drug tolerance
• ligands
• computational science
• molecular dynamics simulations

Subject Categories:

Distribution Statement:

APPROVED FOR PUBLIC RELEASE