Therapeutic strategies for antibiotic development. A to D, Schematic illustration showing the approximate number of factors or requirements that need to be met for different types of therapies illustrating the advantage of multi-target inhibition. A, For an individual drug acting on a single target, there are at least 10 requirements or factors to be satisfied for success. B, Combination therapies involving two new drugs acting on two new targets double the requirements for success. C, Multi-target inhibitors retain the advantages of combination therapies but require fewer properties to be satisfied for success. D, Combination multi-targeting is expected to be highly active and resistance-resistant. E to G, There are three main classes of multi-target inhibitor: series, parallel and network. E, Series inhibitors work on sequential targets in the same metabolic pathway. F, parallel inhibitors work on unrelated pathways (e.g. DNA and membrane targets). G, Network inhibition is a combination of series and parallel inhibitors. H, Hybrid inhibitors contain overlapping or fused pharmacophores for 2 or more targets. E to G are reprinted with permission from reference [35]. Copyright 2014 American Chemical Society.