Medicinal Chemistry, Charles River, Chesterford Park Research Park, Saffron Walden, United Kingdom.
Medicinal Chemistry, Nimbus Therapeutics, Cambridge, MA, USA.
Expert Opin Ther Pat. 2021 Oct;31(10):893-910. doi: 10.1080/13543776.2021.1924671. Epub 2021 May 20.
: Hematopoietic progenitor kinase (HPK1), a serine/threonine kinase, which is primarily expressed in hematopoietic cells is a negative regulator of T-cell receptor and B cell signaling. Studies using genetic disruption of HPK1 function show enhanced T-cell signaling, cytokine production, and tumor growth inhibition. This profile of enhanced immune response highlights small molecule inhibition of HPK1 as an attractive approach for the immunotherapy of cancer.: This article summarizes the biological rationale for the inhibition of HPK1 as a potential adjunct to the current immuno-oncology (IO) therapies. The article primarily discloses the current state of development of HPK1 inhibitors.: The rapid increase in the identification of small molecule inhibitors of HPK1 should translate into a fuller understanding of the role of HPK1 inhibition in the IO setting. This understanding will be of huge importance in determining whether HPK1 inhibition alone will be sufficient for tumor growth inhibition or if combination with current IO therapies will be required.
: 造血祖细胞激酶 (HPK1) 是一种丝氨酸/苏氨酸激酶，主要在造血细胞中表达，是 T 细胞受体和 B 细胞信号的负调节剂。使用 HPK1 功能的遗传破坏研究表明，T 细胞信号增强、细胞因子产生和肿瘤生长抑制。这种增强免疫反应的特征突显了小分子抑制 HPK1 作为癌症免疫治疗的一种有吸引力的方法。: 本文总结了抑制 HPK1 作为当前免疫肿瘤学 (IO) 治疗的潜在辅助治疗的生物学原理。本文主要披露了 HPK1 抑制剂的当前开发状况。: HPK1 小分子抑制剂的快速鉴定应该会更全面地了解 HPK1 抑制在 IO 环境中的作用。这一理解对于确定 HPK1 抑制是否足以抑制肿瘤生长，或者是否需要与当前的 IO 疗法联合使用，将非常重要。
