Development of a Rapid Screening Assay Using Metabolic Inhibitors to Detect Highly Selective Anticancer Agents

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2021 Jul 26

PMID 34308064

Citations 5

Authors

Felagot A Abebe

Megan D Hopkins

Suraj N Vodnala

Robert J Sheaff

Angus A Lamar

Affiliations

Soon will be listed here.

Abstract

Traditional long exposure (24-72 h) cell viability assays for identification of potential drug compounds can fail to identify compounds that are: (a) biologically active but not toxic and (b) inactive without the addition of a synergistic additive. Herein, we report the development of a rapid (1-2 h) compound screening technique using a commercially available cell viability kit (CellTiter-Glo) that has led to the detection of compounds that were not identified as active agents using traditional cytotoxicity screening methods. These compounds, in combination with metabolic inhibitor 2-deoxyglucose, display selectivity toward a pancreatic cancer cell line. An evaluation of 11 mammalian cell lines against 30 novel compounds and two metabolic inhibitors is reported. The inclusion of metabolic inhibitors during an initial screening process, and not simply during mechanistic investigations of a previously identified hit compound, provides a rapid and sensitive tool for identifying drug candidates potentially overlooked by other methods.

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