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Systematic Analysis of Gene Synergies to Discover Drug Synergies

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Predicting synergistic drug interactions

Using synergistic drug interactions allows physicians to decrease individual drug doses while achieving full therapeutic effect. It is important to predict possible drug synergies in order to decrease drug toxicity and reduce the side effects.

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The effects achieved by a synergistic drug pair exceed the cumulative effect of the individual drugs. One of the possible models of drug synergy correlates with synergistic genetic interaction, when drugs target the products of the genes acting in parallel pathways. Termed 'specific synergy', such drug interaction mechanisms differ from 'promiscuous synergy'. Promiscuous, or nonspecific synergy happens when one drug can enhance the action of several drugs in a less specific way, for example through enhancing bioavailability. The 'Systematic analysis of gene synergies to discover drug synergies' (GS2DS) project studied the prevalence of different types of synergy using a panel of antifungal drugs. The team used the yeast, S. cerevisiae as a model as many genetic interactions in it are known. The effects of 200 drug pairs were tested for synergy. While some of the discovered drug synergies were specific and corresponded to synergistic genetic interactions, the majority were of promiscuous type. Six frequently synergistic drugs were responsible for 92 % of the discovered synergies. Overall, 37 new drug synergies along with 93 suppressive drug interactions were found. Promiscuous synergy may have happened due to increased bioavailability through membrane destabilisation. However, the mechanism of two out of six frequently synergistic drugs could not be explained through the bioavailability model and further studies are needed. In the course of the GS2DS project the scientists identified novel synergistic drug pairs possessing antifungal activity. The obtained results advanced understanding of drug interactions and explored possible mechanisms behind them.Drug interactions can have a positive or a negative effect on human health.


Synergistic, drug, interaction, promiscuous synergy, yeast

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