Enhanced interrogation: emerging strategies for cell signaling inhibition.
Here we summarize recent and developing chemical approaches for modulating signaling pathways. In particular, we discuss targeting mutant signaling proteins, disrupting protein-protein interactions in cellular signaling networks, designing bivalent inhibitors of signaling proteins and identifying allosteric regulators of signaling enzymes. Over the past decade, great progress in the harvesting of chemical tools for basic research and clinical medicine has been made, but many challenges remain, and examples of exciting future targets are highlighted.
Department of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Rong
R
Huang
Isabel
I
Martinez-Ferrando
Philip A
PA
Cole
D000494:Allosteric Regulation; D000818:Animals; D006801:Humans; D008954:Models, Biological; D050505:Mutant Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects; D021382:Protein Sorting Signals / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D050505:Mutant Proteins; D021382:Protein Sorting Signals