A Structure-Based Allosteric Modulator Design Paradigm.

Allosteric drugs bound to topologically distal allosteric sites hold a substantial promise in modulating therapeutic targets deemed undruggable at their orthosteric sites. Traditionally, allosteric modulator discovery has predominantly relied on serendipitous high-throughput screening. Nevertheless, the landscape has undergone a transformative shift due to recent advancements in our understanding of allosteric modulation mechanisms, coupled with a significant increase in the accessibility of allosteric structural data.