Updated patent review for Hematopoietic progenitor kinase (HPK1) inhibitors and degraders (2021-present)

Hematopoietic progenitor cell kinase (HPK1) is a serine/threonine kinase of MAP4K family. It negatively regulates T cell receptor and B cell signal transduction. The loss of HPK1 kinase function increases the secretion of cytokines, and enhances T cell signal transduction, virus clearance and tumor growth inhibition. Therefore, HPK1 is considered as a promising drug target for tumor immunotherapy. This article surveys the patents published since 2021 aiming to analyze the structural features of scaffolds and the patent landscape. It also discusses the recent clinical developments and provides perspectives on the challenges and the future directions. HPK1 kinase is a viable drug target, and there is an increasing number of clinical studies on HPK1 inhibitors. In the clinical research of HPK1 inhibitors, there are mainly two ways: monotherapy and combination therapy. In recent years, HPK1 degraders derived from PROTAC technology has shown promises along with HPK1 inhibitors. It is hopeful that small molecule inhibitors or degraders targeting HPK1 will gain FDA approval for treatment human diseases in the near future. A rapid survey of literature reports using keyword 'HPK1' in SciFinder® search engine yielded about 180 papers since 2021.