Protein:protein interactions are becoming increasingly significant as potential 
drug targets; however, the rational identification of small molecule inhibitors 
of such interactions remains a challenge. Pharmacophore modelling is a popular 
tool for virtual screening of compound libraries, and has previously been 
successfully applied to the discovery of enzymatic inhibitors. However, the 
application of pharmacophore modelling in the field of protein:protein 
interaction inhibitors has historically been considered more of a challenge and 
remains limited. In this review, we explore the interaction mimicry by known 
inhibitors that originate from in vitro screening, demonstrating the validity of 
pharmacophore mapping in the generation of queries for virtual screening. We 
discuss the pharmacophore mapping methods that have been successfully employed 
in the discovery of first-in-class inhibitors. These successful cases 
demonstrate the usefulness of a "tool kit" of diverse strategies for application 
across a range of situations depending on the available structural information.