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激酶抑制剂在病毒感染管理中的应用新进展。

Recent Developments in the Use of Kinase Inhibitors for Management of Viral Infections.

机构信息

Medicinal Chemistry Division,CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.

Academy of Scientific & Innovative Research, Ghaziabad 201002, India.

出版信息

J Med Chem. 2022 Jan 27;65(2):893-921. doi: 10.1021/acs.jmedchem.0c01467. Epub 2021 Feb 4.

Abstract

Kinases are a group of therapeutic targets involved in the progression of numerous diseases, including cancer, rheumatoid arthritis, Alzheimer's disease, and viral infections. The majority of approved antiviral agents are inhibitors of virus-specific targets that are encoded by individual viruses. These inhibitors are narrow-spectrum agents that can cause resistance development. Viruses are dependent on host cellular proteins, including kinases, for progression of their life-cycle. Thus, targeting kinases is an important therapeutic approach to discovering broad-spectrum antiviral agents. As there are a large number of FDA approved kinase inhibitors for various indications, their repurposing for viral infections is an attractive and time-sparing strategy. Many kinase inhibitors, including baricitinib, ruxolitinib, imatinib, tofacitinib, pacritinib, zanubrutinib, and ibrutinib, are under clinical investigation for COVID-19. Herein, we discuss FDA approved kinase inhibitors, along with a repertoire of clinical/preclinical stage kinase inhibitors that possess antiviral activity or are useful in the management of viral infections.

摘要

激酶是一组参与多种疾病(包括癌症、类风湿性关节炎、阿尔茨海默病和病毒感染)进展的治疗靶点。大多数已批准的抗病毒药物是针对个别病毒编码的病毒特异性靶点的抑制剂。这些抑制剂是窄谱药物,可能导致耐药性的产生。病毒依赖于宿主细胞蛋白,包括激酶,来完成其生命周期。因此,靶向激酶是发现广谱抗病毒药物的重要治疗方法。由于有大量针对各种适应症的 FDA 批准的激酶抑制剂,将其重新用于病毒感染是一种有吸引力且节省时间的策略。许多激酶抑制剂,包括巴瑞替尼、芦可替尼、伊马替尼、托法替尼、帕克里替尼、泽布替尼和伊布替尼,都在临床研究中用于治疗 COVID-19。本文讨论了 FDA 批准的激酶抑制剂,以及一系列具有抗病毒活性或在病毒感染管理中有用的临床/临床前阶段的激酶抑制剂。

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