乳酸脱氢酶抑制剂的专利综述（2014-至今）
A patent review of lactate dehydrogenase inhibitors (2014-present)
影响因子:4.60000
分区:医学2区 / 药物化学2区 药学2区
发表日期:2024 Nov
作者:
Giulia Bononi, Valeria Di Bussolo, Tiziano Tuccinardi, Filippo Minutolo, Carlotta Granchi
摘要
乳酸脱氢酶（LDH）是糖酵解的关键酶，负责丙酮酸转化为乳酸，反之亦然。乳酸在肿瘤进展和转移中起着至关重要的作用。因此，通过抑制LDH来减少乳酸的产生被认为是解决癌症的最佳策略。此外，LDH活性的失调与其他病理相关，例如心血管和神经退行性疾病以及原发性高氧钙，纤维化和隐孢子虫病。因此，LDH抑制剂可以作为治疗这些病理状况的潜在治疗剂。本评论涵盖了自2014年以来发布的专利，直到ESPACENET数据库中的现在，涉及LDH抑制剂及其潜在的治疗应用。除了过去的10年，不同的化合物已被确定为LDH抑制剂。其中一些是从已知的LDH抑制剂（例如吡唑基衍生物，喹啉3-磺酰胺）的化学优化得出的，而另一些则属于新近鉴定的LDH抑制剂的化学类别。 LDH抑制作用已被证明是一种有希望的治疗策略，不仅用于预防人类病理，而且是治疗动物疾病的一种有希望的治疗策略。来自学术界和制药行业的已发表专利凸显了科学界在开发有效的LDH抑制剂方面的持续高度兴趣。
Abstract
Lactate dehydrogenase (LDH) is a key enzyme in glycolysis responsible for the conversion of pyruvate into lactate and vice versa. Lactate plays a crucial role in tumor progression and metastasis; therefore, reducing lactate production by inhibiting LDH is considered an optimal strategy to tackle cancer. Additionally, dysregulation of LDH activity is correlated with other pathologies, such as cardiovascular and neurodegenerative diseases as well as primary hyperoxaluria, fibrosis and cryptosporidiosis. Hence, LDH inhibitors could serve as potential therapeutics for treating these pathological conditions.This review covers patents published since 2014 up to the present in the Espacenet database, concerning LDH inhibitors and their potential therapeutic applications.Over the past 10 years, different compounds have been identified as LDH inhibitors. Some of them are derived from the chemical optimization of already known LDH inhibitors (e.g. pyrazolyl derivatives, quinoline 3-sulfonamides), while others belong to newly identified chemical classes of LDH inhibitors. LDH inhibition has proven to be a promising therapeutic strategy not only for preventing human pathologies, but also for treating animal diseases. The published patents from both academia and the pharmaceutical industry highlight the persistent high interest of the scientific community in developing efficient LDH inhibitors.