Yeast-based high-throughput screens for discovery of kinase inhibitors for neglected diseases

Adv Protein Chem Struct Biol. 2021:124:275-309. doi: 10.1016/bs.apcsb.2020.09.007. Epub 2020 Nov 9.

Abstract

The discovery and development of a new drug is a complex, time consuming and costly process that typically takes over 10 years and costs around 1 billion dollars from bench to market. This scenario makes the discovery of novel drugs targeting neglected tropical diseases (NTDs), which afflict in particular people in low-income countries, prohibitive. Despite the intensive use of High-Throughput Screening (HTS) in the past decades, the speed with which new drugs come to the market has remained constant, generating doubts about the efficacy of this approach. Here we review a few of the yeast-based high-throughput approaches that can work synergistically with parasite-based, in vitro, or in silico methods to identify and optimize novel antiparasitic compounds. These yeast-based methods range from HTP screens to identify novel hits against promising parasite kinase targets to the identification of potential antiparasitic kinase inhibitors extracted from databases of yeast chemical genetic screens.

Keywords: Drug discovery; Drug screening; High-throughput; Kinase inhibitors; Neglected diseases; Yeast.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Drug Discovery*
  • Drug Evaluation, Preclinical
  • Humans
  • Neglected Diseases* / drug therapy
  • Neglected Diseases* / enzymology
  • Neglected Diseases* / genetics
  • Protein Kinase Inhibitors* / chemistry
  • Protein Kinase Inhibitors* / therapeutic use
  • Protein Kinases* / genetics
  • Protein Kinases* / metabolism
  • Saccharomyces cerevisiae* / enzymology
  • Saccharomyces cerevisiae* / genetics

Substances

  • Protein Kinase Inhibitors
  • Protein Kinases