Journal article
Authors list: Preuss, J; Richardson, AD; Pinkerton, A; Hedrick, M; Sergienko, E; Rahlfs, S; Becker, K; Bode, L
Publication year: 2013
Pages: 286-297
Journal: Journal of Biomolecular Screening
Volume number: 18
Issue number: 3
ISSN: 1087-0571
eISSN: 1552-454X
Open access status: Hybrid
DOI Link: https://doi.org/10.1177/1087057112462131
Publisher: SAGE Publications (UK and US)
Abstract:
Glucose-6-phosphate dehydrogenase (G6PD) is the key enzyme of the pentose phosphate pathway, converting glucose-6-phosphate to 6-phosphoglucono-delta-lactone with parallel reduction of NADP+. Several human diseases, including cancer, are associated with increased G6PD activity. To date, only a few G6PD inhibitors have been available. However, adverse side effects and high IC50 values hamper their use as therapeutics and basic research probes. In this study, we developed a high-throughput screening assay to identify novel human G6PD (hG6PD) inhibitors. Screening the LOPAC (Sigma-Aldrich; 1280 compounds), Spectrum (Microsource Discovery System; 1969 compounds), and DIVERSet (ChemBridge; 49 971 compounds) small-molecule compound collections revealed 139 compounds that presented >= 50% hG6PD inhibition. Hit compounds were further included in a secondary and orthogonal assay in order to identify false-positives and to determine IC50 values. The most potent hG6PD inhibitors presented IC50 values of <4 mu M. Compared with the known hG6PD inhibitors dehydroepiandrosterone and 6-aminonicotinamide, the inhibitors identified in this study were 100- to 1000-fold more potent and showed different mechanisms of enzyme inhibition. One of the newly identified hG6PD inhibitors reduced viability of the mammary carcinoma cell line MCF10-AT1 (IC50 similar to 25 mu M) more strongly than that of normal MCF10-A cells (IC50 >50 mu M).
Citation Styles
Harvard Citation style: Preuss, J., Richardson, A., Pinkerton, A., Hedrick, M., Sergienko, E., Rahlfs, S., et al. (2013) Identification and Characterization of Novel Human Glucose-6-Phosphate Dehydrogenase Inhibitors, Journal of Biomolecular Screening, 18(3), pp. 286-297. https://doi.org/10.1177/1087057112462131
APA Citation style: Preuss, J., Richardson, A., Pinkerton, A., Hedrick, M., Sergienko, E., Rahlfs, S., Becker, K., & Bode, L. (2013). Identification and Characterization of Novel Human Glucose-6-Phosphate Dehydrogenase Inhibitors. Journal of Biomolecular Screening. 18(3), 286-297. https://doi.org/10.1177/1087057112462131
