乳酸脱氢酶抑制剂的专利综述（2014年至今）
A patent review of lactate dehydrogenase inhibitors (2014-present)
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影响因子:4.6
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
DOI:
10.1080/13543776.2024.2412575
摘要
乳酸脱氢酶（LDH）是糖酵解中的关键酶，负责丙酮酸向乳酸的转化及逆转。乳酸在肿瘤的进展和转移中扮演关键角色，因此，通过抑制LDH降低乳酸生成被视为应对癌症的有效策略。此外，LDH活性的失调与心血管疾病、神经退行性疾病、原发性高草酸血症、纤维化和隐孢子虫病等其他疾病相关。因此，LDH抑制剂有望成为治疗这些疾病的潜在药物。本综述涵盖自2014年以来在Espacenet数据库中发表的关于LDH抑制剂及其潜在治疗应用的专利。过去十年中，已发现多种化合物作为LDH抑制剂，其中一些源于对已知LDH抑制剂（如吡唑衍生物、喹啉-3-磺酰胺）的化学优化，另一些则属于新发现的化学类别。LDH抑制已被证明是预防人类疾病及治疗动物疾病的有潜力的策略。来自学术界和制药行业的专利显示，科学界持续对开发高效LDH抑制剂保持浓厚兴趣。
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.