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Peer-reviewedCC BYJournal of enzyme inhibition and medicinal chemistry

Research progress on ATP-citrate lyase and its inhibitors: a metabolic-epigenetic perspective.

  • Qinglin Liu1
  • Hongbin Sun1,2
  • Liang Dai1,2
  1. 1Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China.
  2. 2Chongqing Innovation Institute of China Pharmaceutical University, Chongqing, China.
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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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Cite

BibTeXRIS
BibTeX
@article{liu2026research,
  title = {{Research progress on ATP-citrate lyase and its inhibitors: a metabolic-epigenetic perspective.}},
  author = {Qinglin Liu and Hongbin Sun and Liang Dai},
  journal = {Journal of enzyme inhibition and medicinal chemistry},
  year = {2026},
  month = oct,
  doi = {10.1080/14756366.2026.2744392},
  url = {https://europepmc.org/article/MED/42875375},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Research progress on ATP-citrate lyase and its inhibitors: a metabolic-epigenetic perspective.
AU  - Qinglin Liu
AU  - Hongbin Sun
AU  - Liang Dai
PY  - 2026
DA  - 2026/10/14
JO  - Journal of enzyme inhibition and medicinal chemistry
DO  - 10.1080/14756366.2026.2744392
UR  - https://europepmc.org/article/MED/42875375
AB  - 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.
SN  - 1475-6366
SN  - 1475-6374
ER  -