Development of Allosteric Modulators: Beyond Orthosteric Binding

Abstract

The advent of allosteric modulators has revolutionized drug development as it has advantages that are additional to the orthosteric binding sites. These modulators change the function of a protein in some non-conventional ways through their site selective non-competitive interactions leading to improved selectivity and lesser side effects. The search for allosteric sites has been spurred by the emergence of multi-omics, artificial intelligence and structural biology. This opens the door to targeted treatment of complex diseases in cancers, neurodegeneration and metabolic disorders. In this work, we describe the novel mechanism of action, therapeutical value and perspectives for development of allosteric modulators as a way to expand the druggable targets and the scope of eventual precision medicine.