Clinical Research Institution, the First Affiliated Hospital, and School of Medicine, University of South China, Hengyang, Hunan, PR China.
Recent Pat Anticancer Drug Discov. 2012 May 1;7(2):154-67. doi: 10.2174/157489212799972954.
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.
三磷酸腺苷柠檬酸裂解酶（ATP citrate lyase，ACL 或 ACLY）是一种广泛分布于各种人和动物组织中的线粒体外酶。ACL 在存在 ATP 和 CoA 的情况下，可催化糖酵解产生的柠檬酸生成乙酰辅酶 A 和草酰乙酸，从而连接葡萄糖和脂质代谢。ACL 在许多永生化细胞和肿瘤中异常表达，如乳腺癌、肝癌、结肠癌、肺癌和前列腺癌，并且与肿瘤分期和分化呈负相关，是一种不良预后标志物。ACL 是长链脂肪酸合成的上游酶，提供乙酰辅酶 A 作为脂肪酸合成的必需成分。因此，ACL 是细胞脂肪生成的关键酶，也是癌症治疗的有效靶点。作为代谢综合征和癌症治疗的降血脂策略，已经设计和开发了许多针对 ACL 的小分子化学物质。本文综述了 ACL 抑制剂的研究和开发进展，重点介绍了它们的专利状况，为它们的潜在应用提供了新的见解。
