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

Author(s)

Tavella, T. A. ; Cassiano, G. C. ; Maranhao Costa, Fabio Trindade ; Sunnerhagen, P. ; Bilsland, E. ; Donev, R

• Document type: Journal article
• Source: ADVANCES IN PROTEIN CHEMISTRY AND STRUCTURAL BIOLOGY, VOL 124: PROTEIN KINASES IN DRUG DISCOVERY; v. 124, p. 35-pg., 2021-01-01.

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. (AU)

• FAPESP's process: 19/27626-3 - Identification of new antimalarial compounds for target-centered drug repositioning approach
• Grantee: Tatyana Almeida Tavella
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/20774-6 - Identifying protein kinase inhibitors as antimalarial agents using chemogenomic, bioinfomatics and phenotypic strategies: focus in Plasmodium vivax.
• Grantee: Gustavo Capatti Cassiano
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/16525-2 - Plasmodium vivax: pathogenesis and infectivity
• Grantee: Fabio Trindade Maranhão Costa
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/03553-6 - Engineering yeast cells for drug discovery
• Grantee: Elizabeth Bilsland
• Support Opportunities: Research Grants - Young Investigators Grants