ATP citrate lyase (ACLY) is a cytosolic homotetrameric enzyme that catalyzes the conversion of citrate and coenzyme A (CoA) to acetyl-CoA and oxaloacetate, with the simultaneous hydrolysis of ATP to ADP and phosphate. Interestingly, ACLY is a strategic enzyme linking both the glycolytic and lipidic metabolism. In tumour cells characterized by an altered energetic metabolism, an increased glucose uptake and an accelerated glycolytic flux lead to an intensified production of mitochondrial citrate. Once transported to the cytosol, citrate is here converted by ACLY to acetyl-CoA, an essential biosynthetic precursor for fatty acid synthesis and mevalonate pathway. ACLY expression and activity proved to be aberrantly expressed in many types of tumours, and its pharmacological or genetic inhibition significantly inhibited cancer cell proliferation and induced apoptosis. Increasing evidences highlight the central role of ACLY, conferring a great therapeutic potential to this enzyme as a key target for the treatment of cancer. ACLY inhibitors, previously developed for metabolic disorders, have recently attracted interest as promising anti-cancer agents. After a brief introduction to the structure and the pathophysiological role of ACLY, this review article provides an overview of the main ACLY inhibitors reported in the literature.

ATP柠檬酸裂合酶（ACLY）是一种胞质同型四聚体酶，可催化柠檬酸和辅酶A（CoA）转化为乙酰辅酶A和草酰乙酸，同时将ATP水解为ADP和磷酸盐。有趣的是，ACLY是连接糖酵解和脂质代谢的战略酶。在以高能代谢改变为特征的肿瘤细胞中，葡萄糖摄取增加和糖酵解通量加速导致柠檬酸线粒体产生增加。柠檬酸盐一旦转运到细胞质中，就会被ACLY转化为乙酰辅酶A，乙酰辅酶A是脂肪酸合成和甲羟戊酸途径必不可少的生物合成前体。事实证明，ACLY的表达和活性在许多类型的肿瘤中均异常表达，其药理或遗传抑制作用显着抑制癌细胞增殖并诱导细胞凋亡。越来越多的证据凸显了ACLY的核心作用，使这种酶具有巨大的治疗潜力，成为治疗癌症的关键靶标。先前针对代谢疾病开发的ACLY抑制剂最近作为有希望的抗癌药引起了人们的兴趣。在简要介绍了ACLY的结构和病理生理作用后，本文综述了文献中报道的主要ACLY抑制剂。最近，作为有前途的抗癌药物引起了人们的兴趣。在简要介绍了ACLY的结构和病理生理作用后，本文综述了文献中报道的主要ACLY抑制剂。最近，作为有前途的抗癌药物引起了人们的兴趣。在简要介绍了ACLY的结构和病理生理作用后，本文综述了文献中报道的主要ACLY抑制剂。