Hematopoietic Progenitor Kinase 1 in Tumor Immunology: A Medicinal Chemistry Perspective,Journal of Medicinal Chemistry

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Hematopoietic Progenitor Kinase 1 in Tumor Immunology: A Medicinal Chemistry Perspective
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2022-06-13 , DOI: 10.1021/acs.jmedchem.2c00172
Qiangsheng Zhu ₁ , Nannan Chen ₁ , Xinjian Tian ₁ , Yeling Zhou ₁ , QiDong You ₁ , Xiaoli Xu ₁

Affiliation

Hematopoietic progenitor kinase 1 (HPK1), a hematopoietic cell-restricted member of the serine/threonine Ste20-related protein kinases, is a negative regulator of the T cell receptor, B cell receptor, and dendritic cells. Loss of HPK1 kinase function increases cytokine secretion and enhances T cell signaling, virus clearance, and tumor growth inhibition. Therefore, HPK1 is considered a promising target for tumor immunotherapy. Several HPK1 inhibitors have been reported to regulate T cell function. In addition, HPK1-targeting PROTACs, which can induce the degradation of HPK1, have also been developed. Here, we provide an overview of research concerning HPK1 protein structure, function, and inhibitors and propose perspectives and insights for the future development of agents targeting HPK1.

中文翻译：

肿瘤免疫学中的造血祖细胞激酶 1：药物化学视角

造血祖细胞激酶 1 (HPK1) 是丝氨酸/苏氨酸 Ste20 相关蛋白激酶的造血细胞限制性成员，是 T 细胞受体、B 细胞受体和树突细胞的负调节剂。HPK1 激酶功能的丧失会增加细胞因子分泌并增强 T 细胞信号传导、病毒清除和肿瘤生长抑制。因此，HPK1被认为是肿瘤免疫治疗的有希望的靶点。据报道，几种 HPK1 抑制剂可调节 T 细胞功能。此外，还开发了可诱导 HPK1 降解的 HPK1 靶向 PROTAC。在这里，我们概述了有关 HPK1 蛋白结构、功能和抑制剂的研究，并为未来开发针对 HPK1 的药物提出了观点和见解。

更新日期：2022-06-13

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