Targeting lysine acetylation readers and writers.

Autor: Zhou MM; Departments of Pharmacological Sciences and Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ming-ming.zhou@mssm.edu., Cole PA; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. pacole@bwh.harvard.edu.; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA. pacole@bwh.harvard.edu.
Jazyk: angličtina
Zdroj: Nature reviews. Drug discovery [Nat Rev Drug Discov] 2024 Nov 21. Date of Electronic Publication: 2024 Nov 21.
DOI: 10.1038/s41573-024-01080-6
Abstrakt: Lysine acetylation is a major post-translational modification in histones and other proteins that is catalysed by the 'writer' lysine acetyltransferases (KATs) and mediates interactions with bromodomains (BrDs) and other 'reader' proteins. KATs and BrDs play key roles in regulating gene expression, cell growth, chromatin structure, and epigenetics and are often dysregulated in disease states, including cancer. There have been accelerating efforts to identify potent and selective small molecules that can target individual KATs and BrDs with the goal of developing new therapeutics, and some of these agents are in clinical trials. Here, we summarize the different families of KATs and BrDs, discuss their functions and structures, and highlight key advances in the design and development of chemical agents that show promise in blocking the action of these chromatin proteins for disease treatment.
Competing Interests: Competing interests: M.M.Z. is a founder, director and shareholder of Parkside Scientific Inc. P.A.C. was a founder, adviser, and equity holder of Acylin Therapeutics and has been a consultant for Abbvie Inc., Constellation Pharmaceuticals (now MorphoSys) and Epizyme (now Ipsen).
(© 2024. Springer Nature Limited.)
Databáze: MEDLINE
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