2. Academic Validation
  3. Computational Cell Cycle Profiling of Cancer Cells for Prioritizing FDA-Approved Drugs with Repurposing Potential

Computational Cell Cycle Profiling of Cancer Cells for Prioritizing FDA-Approved Drugs with Repurposing Potential

  • Sci Rep. 2017 Sep 12;7(1):11261. doi: 10.1038/s41598-017-11508-2.
Yu-Chen Lo 1 2,  Silvia Senese 1,  Bryan France 3 4,  Ankur A Gholkar 1,  Robert Damoiseaux 3 4,  Jorge Z Torres 5 6 7
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA.
  • 2 Program in Bioengineering, University of California, Los Angeles, CA 90095, USA.
  • 3 Department of Molecular and Medical Pharmacology, Los Angeles, CA 90095, USA.
  • 4 California NanoSystems Institute, University of California, Los Angeles, CA 90095, USA.
  • 5 Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA. torres@chem.ucla.edu.
  • 6 Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USA. torres@chem.ucla.edu.
  • 7 Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA. torres@chem.ucla.edu.
PMID: 28900159 DOI: 10.1038/s41598-017-11508-2
Abstract

Discovery of first-in-class medicines for treating Cancer is limited by concerns with their toxicity and safety profiles, while repurposing known drugs for new Anticancer indications has become a viable alternative. Here, we have developed a new approach that utilizes cell cycle arresting patterns as unique molecular signatures for prioritizing FDA-approved drugs with repurposing potential. As proof-of-principle, we conducted large-scale cell cycle profiling of 884 FDA-approved drugs. Using cell cycle indexes that measure changes in cell cycle profile patterns upon chemical perturbation, we identified 36 compounds that inhibited Cancer cell viability including 6 compounds that were previously undescribed. Further cell cycle fingerprint analysis and 3D chemical structural similarity clustering identified unexpected FDA-approved drugs that induced DNA damage, including clinically relevant microtubule destabilizers, which was confirmed experimentally via cell-based assays. Our study shows that computational cell cycle profiling can be used as an approach for prioritizing FDA-approved drugs with repurposing potential, which could aid the development of Cancer therapeutics.

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