title: ATP citrate lyase inhibitors as novel cancer therapeutic agents.
abstract: ATP citrate lyase (ACL or ACLY) is an extra-mitochondrial enzyme widely distributed in various human and animal tissues. ACL links glucose and lipid metabolism by catalyzing the formation of acetyl-CoA and oxaloacetate from citrate produced by glycolysis in the presence of ATP and CoA. ACL is aberrantly expressed in many immortalized cells and tumors, such as breast, liver, colon, lung and prostate cancers, and is correlated reversely with tumor stage and differentiation, serving as a negative prognostic marker. ACL is an upstream enzyme of the long chain fatty acid synthesis, providing acetyl-CoA as an essential component of the fatty acid synthesis. Therefore, ACL is a key enzyme of cellular lipogenesis and potent target for cancer therapy. As a hypolipidemic strategy of metabolic syndrome and cancer treatment, many small chemicals targeting ACL have been designed and developed. This review article provides an update for the research and development of ACL inhibitors with a focus on their patent status, offering a new insight into their potential application.
authors.affiliation: Clinical Research Institution, the First Affiliated Hospital, and School of Medicine, University of South China, Hengyang, Hunan, PR China.
authors.forename: Xu-Yu
authors.initials: XY
authors.lastname: Zu
authors.forename: Qing-Hai
authors.initials: QH
authors.lastname: Zhang
authors.forename: Jiang-Hua
authors.initials: JH
authors.lastname: Liu
authors.forename: Ren-Xian
authors.initials: RX
authors.lastname: Cao
authors.forename: Jing
authors.initials: J
authors.lastname: Zhong
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Yi
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Quan
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pizzorno
mesh_terms: D001275:ATP Citrate (pro-S)-Lyase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D019343:Citric Acid / Q000031:analogs & derivatives; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D050155:Lipogenesis / Q000187:drug effects*; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D010330:Patents as Topic; D011499:Protein Processing, Post-Translational
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D019343:Citric Acid; D001275:ATP Citrate (pro-S)-Lyase