posted on 2021-07-02, 14:09authored byFelagot
A. Abebe, Megan D. Hopkins, Suraj N. Vodnala, Robert J. Sheaff, Angus A. Lamar
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.