Inhibiting CDC42 subfamily to treat diseases
CDC42 proteins have long been considered ‘undruggable’ due to their elevated structural flexibility and shallow binding pockets. However, conformational changes in CDC42 define its functional ‘on’ and ‘off’ states, offering distinct structures for selective target inhibition, which can elicit distinct therapeutic effects.
Disruption of CDC42/effector interaction is a viable strategy for modulating CDC42-mediated signaling.
Additionally, novel allosteric pockets and druggable binding sites in CDC42 open new avenues for drug design.
Targeting multiple CDC42 family members represents a new opportunity to modulate complex signaling pathways in several pathologies.
https://www.cell.com/trends/pharmacological-sciences/fulltext/S0165-6147(26)00088-X
