Cell-based high-throughput screens for the discovery of chemotherapeutic agents.
With modern advances in robotics and data processing, high-throughput screening (HTS) is playing an increasingly growing role in the drug discovery process. The ultimate success of HTS depends upon the development of assays that are robust and reproducible in miniaturized formats, have low false-positive rates, and can identify drugs that offer improvements over those currently on the market. One example of such an assay is the ATAD5-luciferase HTS assay, which identified three antioxidants that could kill cancer cells without inducing mutagenesis. Here we discuss the ATAD5- luciferase assay and expand upon the value of HTS in identifying other potential cancer drugs, focusing on cell-based assays that involve DNA damage or repair pathways.
Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Jennifer T
JT
Fox
Kyungjae
K
Myung
D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification; D000975:Antioxidants / Q000737:chemistry / Q000302:isolation & purification; D002477:Cells / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D055808:Drug Discovery / Q000379:methods*; D057166:High-Throughput Screening Assays; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008904:Miniaturization; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology
C546328:ATAD5 protein, human; D000970:Antineoplastic Agents; D000975:Antioxidants; D004268:DNA-Binding Proteins; D008156:Luciferases; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities