Recent advances in CDC42 subfamily inhibition and therapeutic potential

CDC42 subfamily members of the RHOGTPases exist in either an active or inactive state, each with a distinct but highly flexible structure, making them challenging to target. Abnormal CDC42 activity is linked to various conditions, including cancer, neurological and ophthalmological disorders, skin diseases, and vascular conditions. This has driven increasing interest in developing CDC42 inhibitors, which have recently produced lead compounds demonstrating disease-modifying effects in vivo. In this review, we provide an overview of the physiological functions of CDC42 subfamily members and their emerging roles in disease. We also examine the latest advances in leveraging CDC42's structural features for selective inhibition, analyzing the mode of action and chemical structures of current inhibitors. These insights aim to inform the design of improved molecules with broad therapeutic potential.