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ATP citrate lyase (ACLY) is a key enzyme in cellular metabolism, being the main source of acetyl-Coenzyme A, an important precursor for fatty acid, cholesterol, and isoprenoid biosynthesis, and it is also involved in protein acetylation. Its expression changes are related to hyperlipidemia and cardiovascular diseases. Other studies have shown that ACLY is closely related to the occurrence of cancer: the increase in lipid synthesis provides the necessary building blocks for cell growth and division. Therefore, finding effective ACLY inhibitors has very important application prospects for lipid-related pathologies and cancer. This review covers patents concerning ACLY inhibitors and alternative strategies to modulate ACLY activity, with their potential therapeutic applications. In recent years, ACLY as a drug target has become a hot spot in the research of innovative drugs for disorders of glucose and lipid metabolism. Many types of small-molecule ACLY inhibitors have been discovered, but few ACLY inhibitors proved to be highly effective  in vitro  and  in vivo , since their main limitations were low cell penetration and low affinity to ACLY. The search for new effective ACLY inhibitors is of great significance and has broad application prospects for the treatment of hyperlipidemia and cancer.

ATP-citrate lyase (ACLY) inhibitors as therapeutic agents: a patenting perspective