基于吡嗪的小分子激酶抑制剂：临床应用和专利审查（2019-2023）。
Pyrazine-based small molecule kinase inhibitors: clinical applications and patent review (2019-2023).
发表日期：2024 Aug 27
作者：
Aisha Alsfouk
来源：
Food & Function
摘要：
蛋白激酶在细胞信号通路中发挥着关键作用，包括增殖、凋亡、炎症和免疫调节。因此，用小分子靶向激酶已成为癌症和其他疾病（包括炎症和自身免疫性疾病）的治疗潜力。现有小分子激酶抑制剂的主要化学基序是杂环、含氮环和六元环，包括吡嗪。几种有效的、选择性的基于吡嗪的激酶抑制剂已被开发并进入临床试验。激酶抑制剂的临床应用数据表明，在几种难复发的恶性肿瘤和重度至中度免疫性疾病中，激酶抑制剂具有良好的临床活性和可控制的毒性。所有基于吡嗪的激酶抑制剂均具有口服活性。本文回顾了与吡嗪类小分子抑制剂相关的最新激酶文献（2019-2023）。该审查包括 FDA（食品和药物管理局）批准的专利代理人及其靶向激酶、支架、效力、选择性概况、受让人以及临床和临床前研究中的生物学结果。
Protein kinases play a key role in cellular signaling pathways including proliferation, apoptosis, inflammation and immune regulation. Therefore, targeting kinases with small molecules has emerged as a therapeutic potential in cancers and other diseases including inflammatory and autoimmune disorders. The main chemical motifs of the available small molecule kinase inhibitors are heterocyclic, nitrogen-containing and six-membered rings including pyrazine. Several potent and selective pyrazine-based kinase inhibitors have been developed and progressed into clinical trials. The data of clinical application of kinase inhibitors demonstrate good clinical activity with manageable toxicity in several relapse-resistant malignancies and severe to moderate immunological disorders. All pyrazine-based kinase inhibitors are orally active. This paper reviews the most recent kinase literature (2019-2023) related to pyrazine-based small molecule inhibitors. This review includes the FDA (Food and Drug Administration)-approved and patent agents along with their targeted kinase, scaffold, potency, selectivity profile, assignee and biological results in clinical and preclinical studies.