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RASPELD to Perform High‐End Screening in an Academic Environment toward the Development of Cancer Therapeutics
Author(s) -
Wolle Patrik,
Weisner Jörn,
Keul Marina,
Landel Ina,
Lategahn Jonas,
Rauh Daniel
Publication year - 2018
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800477
Subject(s) - drug discovery , epidermal growth factor receptor , computational biology , identification (biology) , drug development , computer science , regulator , cancer , drug , biology , bioinformatics , pharmacology , biochemistry , genetics , botany , gene
The identification of compounds for dissecting biological functions and the development of novel drug molecules are central tasks that often require screening campaigns. However, the required architecture is cost‐ and time‐intensive. Herein we describe the devices and technologies that comprise a Robotics‐Assisted Screening Platform for Efficient Ligand Discovery (RASPELD), which we set up in an academic laboratory. RASPELD provides semi‐automated high‐end screening, and it can be maintained by graduate students. We demonstrate its successful application in biochemical and cellular screens for the identification and validation of bioactive chemical entities as candidate cancer‐relevant inhibitors. Specifically, we examined the interaction between a transcription factor, Nrf2, and its key regulator, Keap1. We also examined drug‐resistant mutants of the epidermal growth factor receptor (EGFR). Screening campaigns with more than 30 000 compounds were performed in a reasonable period of time. We identified the molecule RSL6586 as a starting point for hit optimization, which is currently ongoing.