Secondary Pharmacology and Off-Target Effects
Secondary pharmacology has been described as off-target pharmacology where a drug interacts with other targets as well as the intended target, and multi-target drug research where drugs can interact effectively with multiple targets increasing the therapeutic efficacy in certain diseases.3^45-49 These effects can provide both beneficial and adverse outcomes, and in some cases these drug qualities define several adverse effects seen with drugs in development and those marketed. Liu and colleagues49 proposed a drug surveillance network for adverse drug reaction prediction through the integration of chemical compound signatures; biological targets including proteins, transporters, and enzymes, along with pathways; and phenotypic properties. Wang and colleagues45 report on a protein pharmacology interaction network database, PhIN, where users can generate interacting target networks within and across human biological pathways by defining shared chemical compounds or scaffolds using a defined activity cutoff. The database also defines interactions between human-virus and virus-virus pathways. The database contains ~1 350 000 compounds; ~9400 targets with more than 12 400 000 activity measurements (as of March 2015). This type of database provides information and evidence-based predictions of chemical structures that interact with multiple targets, which would be useful in multi-target drug design and side effect predictions.