ReviewJournal of enzyme inhibition and medicinal chemistry2026
Research progress on ATP-citrate lyase and its inhibitors: a metabolic-epigenetic perspective.
Review in Journal of enzyme inhibition and medicinal chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
ATP-citrate lyase (ACLY) is a key enzyme in cellular metabolism that catalyses the cleavage of citrate to produce acetyl coenzyme A (acetyl-CoA), thereby bridging energy metabolism and epigenetic regulation. Acetyl-CoA serves as a common substrate for de novo lipogenesis (DNL) and histone acetylation. Aberrant ACLY activity is closely associated with various pathological conditions, including metabolic diseases, Immune-mediated inflammatory diseases (IMIDs), cancer, and neurodegenerative diseases, positioning ACLY as an important therapeutic target for these diseases. However, existing inhibitors face challenges such as insufficient selectivity and limited clinical efficacy and off-target effects. This review systematically summarises the molecular mechanisms and pathological significance of ACLY within the overarching framework of its dual metabolic-epigenetic functions, from three perspectives, namely its structure and function, disease relevance, and inhibitor development and optimisation strategies, aiming to provide a theoretical foundation for precision therapies targeting ACLY.
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