Yongjun Zang , Maoying Shi , Luyang Tai , Yuanyang Hu , Yu Wang , Runan Zheng , Zhiqi Feng , Haoliang Yuan , Xiaoan Wen , Liang Dai
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引用次数: 0
Abstract
ATP-citrate lyase (ACLY) is a key lipogenic enzyme involved in the synthesis of fatty acid and cholesterol, which converts cytosolic citrate to acetyl-CoA, a starting material for de novo lipogenesis. ACLY inhibitor is considered as potential therapeutic strategy for dyslipidemia and related diseases. In this study, we reported a series of novel macrocyclic derivatives as ACLY inhibitors, among them, compound 55 exhibited potent ACLY inhibitory activity (IC50 = 8.3 nM) and high binding affinity to ACLY. Notably, compound 55 demonstrated good pharmacokinetic profiles and potent in vivo hypolipidemic effect. Collectively, compound 55 deserved further development to provide potential candidate for treatment of hyperlipidemia and related diseases.
atp -柠檬酸裂解酶（ACLY）是一种关键的脂肪生成酶，参与脂肪酸和胆固醇的合成，将细胞质柠檬酸转化为乙酰辅酶a，这是重新生成脂肪的起始物质。ACLY抑制剂被认为是治疗血脂异常及相关疾病的潜在策略。在本研究中，我们报道了一系列新的大环衍生物作为ACLY抑制剂，其中化合物55具有较强的ACLY抑制活性（IC50 = 8.3 nM）和与ACLY的高结合亲和力。值得注意的是，化合物55表现出良好的药代动力学特征和有效的体内降血脂作用。总之，化合物55值得进一步开发，为治疗高脂血症和相关疾病提供潜在的候选药物。
期刊介绍：
The European Journal of Medicinal Chemistry is a global journal that publishes studies on all aspects of medicinal chemistry. It provides a medium for publication of original papers and also welcomes critical review papers.
A typical paper would report on the organic synthesis, characterization and pharmacological evaluation of compounds. Other topics of interest are drug design, QSAR, molecular modeling, drug-receptor interactions, molecular aspects of drug metabolism, prodrug synthesis and drug targeting. The journal expects manuscripts to present the rational for a study, provide insight into the design of compounds or understanding of mechanism, or clarify the targets.
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