Quantitative high-throughput drug screening method identifies novel anticancer drug candidates
THURSDAY, Jan. 12 (HealthDay News) -- Quantitative high-throughput screening (qHTS) of a large pharmaceutical collection can identify novel agents with anticancer activity, according to a study published online Dec. 14 in the Journal of Clinical Endocrinology & Metabolism.
Lisa Zhang, Ph.D., of the National Cancer Institute in Bethesda, Md., and colleagues used a qHTS approach to identify agents with anticancer activity in thyroid cancer cell lines. Agents were identified from within the National Institutes of Health Chemical Genomic Center's pharmaceutical collection of 2,816 clinically approved drugs and bioactive compounds. Following identification, the results were validated in thyroid cancer cell lines.
The researchers found that the cardiotonic and antiobesity agents were the categories which were most enriched in antiproliferative activity. Sixteen agents were identified with an efficacy of greater than 60 percent and a 50 percent inhibitor concentration in the nanomolar range. The results were validated using two agents, bortezomib and ouabain, in cell lines representing distinct histologic subtypes of thyroid cancer and with distinct mutations. Apoptosis was induced by both agents, and ouabain induced cell cycle arrest.
"To our knowledge, this is the first study to use qHTS of a large drug library to identify candidate drugs for anticancer therapy," the authors write. "Our results indicate such a screening approach can lead to the discovery of novel agents in different therapeutic categories and drugs with nonclassic chemotherapy mode of action. Our approach could lead to drug repurposing and accelerate clinical trials of compounds with well-established pharmacokinetics and toxicity profiles."
Abstract
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