Two small molecules, ZCL278 and AZA197 show promise in influencing protein interactions involving the ras-related protein cell division cycle 42 [Cdc42] to modulate its oncogenic potential
by Muhoza, Djamali; Adams, Paul D.
Cdc42 is a member of the Rho subfamily of Ras-related proteins, which were among the first oncogenic proteins to be identified as playing a significant role in a variety of cellular events [Barbacaid, 1987, Ann. Equally important, Protein-Protein Interactions [PPIs] involving Cdc42 continue to highlight the role of Ras-related proteins' relevance to cancer. As these proteins have been considered incapable of being "druggable", due to a perceived lack of binding surface[s] that are amenable to small mol. targeting, there remains limited development of therapies to tackle diseased states caused by Cdc42-stimulated hyperactivity. Thusly, it has become important to characterize mol. details, including dynamics, of PPIs involving Cdc42 that may lend themselves as potential targets for therapeutic approaches. Recently, two small mols., ZCL278 and AZA197, have shown promise in directly targeting Cdc42 to influence PPIs that are capable of causing Cdc42-stimulated abnormal signaling. In this editorial, we highlight recent studies that show case how these two small mols. may influence Cdc42-protein interactions.