Di Stefano Giuseppina, Manerba Marcella, Di Ianni Lorenza, Fiume Luigi
Department of Experimental, Diagnostic & Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
Future Med Chem. 2016 Apr;8(6):713-25. doi: 10.4155/fmc.16.10. Epub 2016 Apr 7.
Lactate dehydrogenase (LDH) inhibition is considered a worthwhile attempt in the development of innovative anticancer strategies. Unfortunately, in spite of the involvement of several research institutions and pharma-companies, the discovery of LDH inhibitors with drug-like properties seems a hardly resolvable challenge. While awaiting new advancements, in the present review we will examine other pathologic conditions characterized by increased glycolysis and LDH activity, which could potentially benefit from LDH inhibition. The rationale for targeting LDH activity in these contexts is the same justifying the LDH-based approach in anticancer therapy: because of the enzyme position at the end of glycolytic pathway, LDH inhibitors are not expected to hinder glucose metabolism of normal cells. Moreover, we will summarize the latest contributions in the discovery of enzyme inhibitors and try to glance over the reasons underlying the complexity of this research.
乳酸脱氢酶（LDH）抑制被认为是开发创新抗癌策略的一项有价值的尝试。不幸的是，尽管有多个研究机构和制药公司参与其中，但发现具有类药物性质的LDH抑制剂似乎是一个难以解决的挑战。在等待新进展的同时，在本综述中，我们将研究其他以糖酵解增加和LDH活性升高为特征的病理状况，这些状况可能会从LDH抑制中受益。在这些情况下靶向LDH活性的基本原理与在抗癌治疗中采用基于LDH的方法的理由相同：由于该酶位于糖酵解途径的末端，预计LDH抑制剂不会阻碍正常细胞的葡萄糖代谢。此外，我们将总结酶抑制剂发现方面的最新贡献，并试图审视这项研究复杂性背后的原因。
