Diagonal method to measure synergy among any number of drugs

Çokol-Çakmak, Melike and Bakan, Feray and Çetiner, Selim and Çokol, Murat (2018) Diagonal method to measure synergy among any number of drugs. Journal of Visualized Experiments (JoVE), 2018 (136). ISSN 1940-087X

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A synergistic drug combination has a higher efficacy compared to the effects of individual drugs. Checkerboard assays, where drugs are combined in many doses, allow sensitive measurement of drug interactions. However, these assays are costly and do not scale well for measuring interaction among many drugs. Several recent studies have reported drug interaction measurements using a diagonal sampling of the traditional checkerboard assay. This alternative methodology greatly decreases the cost of drug interaction experiments and allows interaction measurement for combinations with many drugs. Here, we describe a protocol to measure the three pairwise interactions and one three-way interaction among three antibiotics in duplicate, in five days, using only three 96-well microplates and standard laboratory equipment. We present representative results showing that the three-antibiotic combination of Levofloxacin + Nalidixic Acid + Penicillin G is synergistic. Our protocol scales up to measure interactions among many drugs and in other biological contexts, allowing for efficient screens for multi-drug synergies against pathogens and tumors.
Item Type: Article
Uncontrolled Keywords: Biology; Checkerboard assay; Drug combinations; Drug interactions; Drug synergy; High-order drug interactions; Issue 136; Loewe additivity model
Subjects: Q Science > Q Science (General)
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Biological Sciences & Bio Eng.
Faculty of Engineering and Natural Sciences
Depositing User: Selim Çetiner
Date Deposited: 16 Aug 2018 11:20
Last Modified: 30 May 2023 12:33
URI: https://research.sabanciuniv.edu/id/eprint/35670

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