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将 JAK 转化为 Jakinibs。

Translating JAKs to Jakinibs.

机构信息

Translational Immunology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.

Molecular Immunology and Inflammation Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.

出版信息

J Immunol. 2020 Apr 15;204(8):2011-2020. doi: 10.4049/jimmunol.1901477.

Abstract

The discovery of JAKs and STATs and their roles in cytokine and IFN action represented a significant basic advance and a new paradigm in cell signaling. This was quickly followed by discoveries pointing to their essential functions, including identification of mutations as a cause of SCID. This and other findings predicted the use of therapeutically targeting JAKs as a new strategy for treating immune and inflammatory diseases. This now is a reality with seven approved jakinibs being used to treat multiple forms of arthritis, inflammatory bowel disease and myeloproliferative neoplasms, and numerous ongoing clinical trials in other settings. This story provides interesting insights into the process of translating basic discoveries and also reveals the need to return to basic work to fill gaps that now become apparent.

摘要

JAKs 和 STATs 的发现及其在细胞因子和 IFN 作用中的作用代表了细胞信号转导的重大基础进展和新范例。这之后很快就发现了它们的重要功能,包括鉴定出突变是 SCID 的一个原因。这一发现和其他发现预测了使用靶向 JAK 的治疗方法作为治疗免疫和炎症性疾病的新策略。这一策略现在已经成为现实,有七种已批准的 jakinibs 被用于治疗多种形式的关节炎、炎症性肠病和骨髓增生性肿瘤,并且在其他情况下还有许多正在进行的临床试验。这个故事为我们提供了有趣的见解,让我们了解到将基础发现转化为实际应用的过程,同时也揭示了需要回到基础工作中,以填补现在已经变得明显的空白。

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