For last few decades, the active site cleft and substrate-binding site of enzymes as well as ligand-binding site of the receptors have served as the main pharmacological space for drug discovery. However, rapid accumulation of proteome and protein network analysis data has opened a new therapeutic space that is the interface between the interacting proteins. Due to the complexity of the interaction modes and the numbers of the participating components, it is still challenging to identify the chemicals that can accurately control the protein-protein interactions at desire. Nonetheless, the number of chemical drugs and candidates working at the interface of the interacting proteins are rapidly increasing. This review addresses the current case studies and state-of-the-arts in the development of small chemical modulators controlling the interactions of the proteins that have pathological implications in various human diseases such as cancer, immune disorders, neurodegenerative and infectious diseases.
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