A High-Throughput Yeast Assay Identifies Synergistic Drug Combinations

2013 ◽  
Vol 11 (5) ◽  
pp. 299-307 ◽  
Author(s):  
Nikko P. Torres ◽  
Anna Y. Lee ◽  
Guri Giaever ◽  
Corey Nislow ◽  
Grant W. Brown
Keyword(s):  
High Throughput ◽  
Drug Combinations ◽  
Yeast Assay ◽  
Synergistic Drug Combinations

scholarly journals Synergistic Drug Combinations for Tuberculosis Therapy Identified by a Novel High-Throughput Screen

2011 ◽  
Vol 55 (8) ◽  
pp. 3861-3869 ◽  
Author(s):  
Santiago Ramón-García ◽  
Carol Ng ◽  
Hilary Anderson ◽  
Joseph D. Chao ◽  
Xingji Zheng ◽  
...  
Keyword(s):  
High Throughput ◽  
Bacterial Infections ◽  
Drug Combinations ◽  
Tb Treatment ◽  
Resistant Strains ◽  
Pharmaceutical Properties ◽  
Tuberculosis Therapy ◽  
Drug Resistant Strains ◽  
Synergistic Drug Combinations

ABSTRACTTherapeutic options for tuberculosis (TB) are limited and notoriously ineffective despite the wide variety of potent antibiotics available for treating other bacterial infections. We investigated an approach that enables an expansion of TB therapeutic strategies by using synergistic combinations of drugs. To achieve this, we devised a high-throughput synergy screen (HTSS) of chemical libraries having known pharmaceutical properties, including thousands that are clinically approved. Spectinomycin was used to test the concept that clinically available antibiotics with limited efficacy againstMycobacterium tuberculosismight be used for TB treatment when coadministered with a synergistic partner compound used as a sensitizer. Screens usingMycobacterium smegmatisrevealed many compounds in our libraries that acted synergistically with spectinomycin. Among them, several families of antimicrobial compounds, including macrolides and azoles, were also synergistic againstM. tuberculosis in vitroand in a macrophage model ofM. tuberculosisinfection. Strikingly, each sensitizer identified for synergy with spectinomycin uniquely enhanced the activities of other clinically used antibiotics, revealing a remarkable number of unexplored synergistic drug combinations. HTSS also revealed a novel activity for bromperidol, a butyrophenone used as an antipsychotic drug, which was discovered to be bactericidal and greatly enhanced the activities of several antibiotics and drug combinations againstM. tuberculosis. Our results suggest that many compounds in the currently available pharmacopoeia could be readily mobilized for TB treatment, including disease caused by multi- and extensively drug-resistant strains for which there are no effective therapies.

scholarly journals Biomolecular Network-Based Synergistic Drug Combination Discovery

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Xiangyi Li ◽  
Guangrong Qin ◽  
Qingmin Yang ◽  
Lanming Chen ◽  
Lu Xie
Keyword(s):  
Drug Combination ◽  
Complex Disease ◽  
Recent Decade ◽  
Drug Combinations ◽  
Network Medicine ◽  
Disease Therapy ◽  
Biomolecular Network ◽  
Disease Related Genes ◽  
Disease Specific ◽  
Synergistic Drug Combinations

Drug combination is a powerful and promising approach for complex disease therapy such as cancer and cardiovascular disease. However, the number of synergistic drug combinations approved by the Food and Drug Administration is very small. To bridge the gap between urgent need and low yield, researchers have constructed various models to identify synergistic drug combinations. Among these models, biomolecular network-based model is outstanding because of its ability to reflect and illustrate the relationships among drugs, disease-related genes, therapeutic targets, and disease-specific signaling pathways as a system. In this review, we analyzed and classified models for synergistic drug combination prediction in recent decade according to their respective algorithms. Besides, we collected useful resources including databases and analysis tools for synergistic drug combination prediction. It should provide a quick resource for computational biologists who work with network medicine or synergistic drug combination designing.

Abstract 1053: A large cellular screen charting the landscape of synergistic drug combinations in lung cancer

2021 ◽  
Author(s):  
Nishanth Ulhas Nair ◽  
Adam Friedman ◽  
Patricia Greninger ◽  
Avinash D. Sahu ◽  
Ellen Murchie ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Combinations ◽  
Synergistic Drug Combinations

scholarly journals High-Throughput 3D Tumor Spheroid Array Platform for Evaluating Sensitivity of Proton-Drug Combinations

2022 ◽  
Vol 23 (2) ◽  
pp. 587
Author(s):  
Dong Woo Lee ◽  
Jung Eun Kim ◽  
Ga-Haeng Lee ◽  
Arang Son ◽  
Hee Chul Park ◽  
...  
Keyword(s):  
Cell Lines ◽  
High Throughput ◽  
High Throughput Screening ◽  
Quantitative Data ◽  
Survival Rates ◽  
Drug Combinations ◽  
Targeted Drugs ◽  
Tumor Spheroid ◽  
Array Platform ◽  
Hnscc Cell

Proton beam therapy (PBT) is a critical treatment modality for head and neck squamous cell carcinoma (HNSCC). However, not much is known about drug combinations that may improve the efficacy of PBT. This study aimed to test the feasibility of a three-dimensional (3D) tumor-spheroid-based high-throughput screening platform that could assess cellular sensitivity against PBT. Spheroids of two HNSCC cell lines—Fadu and Cal27—cultured with a mixture of Matrigel were arrayed on a 384-pillar/well plate, followed by exposure to graded doses of protons or targeted drugs including olaparib at various concentrations. Calcein staining of HNSCC spheroids revealed a dose-dependent decrease in cell viability for proton irradiation or multiple targeted drugs, and provided quantitative data that discriminated the sensitivity between the two HNSCC cell lines. The combined effect of protons and olaparib was assessed by calculating the combination index from the survival rates of 4 × 4 matrices, showing that Cal27 spheroids had greater synergy with olaparib than Fadu spheroids. In contrast, adavosertib did not synergize with protons in both spheroids. Taken together, we demonstrated that the 3D pillar/well array platform was a useful tool that provided rapid, quantitative data for evaluating sensitivity to PBT and drug combinations. Our results further supported that administration of the combination of PBT and olaparib may be an effective treatment strategy for HNSCC patients.

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