Identification of potential inhibitors based on compound proposal contest: Tyrosine-protein kinase Yes as a target

Sci Rep. 2015 Nov 26:5:17209. doi: 10.1038/srep17209.

Abstract

A search of broader range of chemical space is important for drug discovery. Different methods of computer-aided drug discovery (CADD) are known to propose compounds in different chemical spaces as hit molecules for the same target protein. This study aimed at using multiple CADD methods through open innovation to achieve a level of hit molecule diversity that is not achievable with any particular single method. We held a compound proposal contest, in which multiple research groups participated and predicted inhibitors of tyrosine-protein kinase Yes. This showed whether collective knowledge based on individual approaches helped to obtain hit compounds from a broad range of chemical space and whether the contest-based approach was effective.

MeSH terms

  • Drug Evaluation, Preclinical*
  • Humans
  • Principal Component Analysis
  • Protein Kinase Inhibitors / analysis*
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins c-yes / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-yes / chemistry
  • Reproducibility of Results
  • src-Family Kinases / metabolism

Substances

  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-yes
  • YES1 protein, human
  • src-Family Kinases