Small-Molecule Modulation of Protein Lipidation: From Chemical Probes to Therapeutics

Protein lipidation is a widespread modification that regulates protein subcellular localization, structure and function. Dysregulation of protein lipidation has been implicated in various human diseases, including neurological disorders, infectious diseases and cancers. Thus lipid-modifying enzymes and their substrate proteins are emerging as attractive drug targets. The development of small-molecule modulators of protein lipidation has remarkably impacted our understanding of lipid-modification biology and potential therapeutics. In this review, we summarize recent progress in small-molecule targeting of protein lipidation and highlight therapeutic opportunities.

Automated summary

Protein lipidation is a widespread modification that regulates protein subcellular localization, structure and function. Dysregulation of protein lipidation has been implicated in various human diseases, and thus lipid-modifying enzymes and substrate proteins are emerging as attractive drug targets. The development of small-molecule modulators of protein lipidation has greatly influenced our understanding of lipid-modification biology and potential therapeutics. In this review, recent progress in small-molecule targeting of protein lipidation is summarized and therapeutic opportunities are highlighted.