Hematopoietic Progenitor Kinase 1 Inhibitors

Authors

  • Zhe Yuan
  • Zhidan Pan

DOI:

https://doi.org/10.54097/kcpmqa71

Keywords:

HPK1 inhibitors; tumor immunotherapy; SAR.

Abstract

Cancer, a general name for wide range of diseases that have the ability to make an impact on any parts of the human body and has been a fatal health issue that affects people around the world. Hematopoietic Progenitor Kinase 1 (HPK1), one member from the MAP4K family, is a kind of serine/threonine kinase. Destruction of HPK1 kinase raises the secretion of cytokine and T cell signaling, having positive impact on clearance of virus, and inhibition of tumor growth. Thus, HPK1 has been seen as a promising target that can be used in drug development for immunotherapy of tumors. HPK1 has a pivotal role of inhibition on the signaling pathway of the T-cell receptor, it also inhibits the proliferation and differentiation of B cells, DC cells, and NK cells. In this paper, we aimed to supply a detailed overview of research including the introduction of HPK1, research process on HPK1 inhibitors and different methods of developing new kinase inhibitors.

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References

Bray, Freddie, et al. "Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries." CA: a cancer journal for clinicians 68.6 (2018): 394-424.

Kim, Ryungsa. "Cancer immunoediting: from immune surveillance to immune escape." Cancer Immunotherapy (2007): 9-27.

Pan, Yang, et al. "RNA dysregulation: an expanding source of cancer immunotherapy targets." Trends in pharmacological sciences 42.4 (2021): 268-282.

Restifo, Nicholas P., Mark J. Smyth, and Alexandra Snyder. "Acquired resistance to immunotherapy and future challenges." Nature Reviews Cancer 16.2 (2016): 121-126.

Sharma, Padmanee, et al. "Primary, adaptive, and acquired resistance to cancer immunotherapy." Cell 168.4 (2017): 707-723.

Dhanak, Dashyant, et al. "Small-molecule targets in immuno-oncology." Cell chemical biology 24.9 (2017): 1148-1160.

Cheng, Binbin, et al. "Recent advances in small molecule-based cancer immunotherapy." European Journal of Medicinal Chemistry 157 (2018): 582-598.

Hernandez, Sairy, et al. "The kinase activity of hematopoietic progenitor kinase 1 is essential for the regulation of T cell function." Cell reports 25.1 (2018): 80-94.

Chuang, Huai-Chia, Xiaohong Wang, and Tse-Hua Tan. "MAP4K family kinases in immunity and inflammation." Advances in immunology 129 (2016): 277-314.

Zhu, Qiangsheng, et al. "Hematopoietic progenitor kinase 1 in tumor immunology: a medicinal chemistry perspective." Journal of Medicinal Chemistry 65.12 (2022): 8065-8090.

Wu, Ping, et al. "Hematopoietic progenitor kinase-1 structure in a domain-swapped dimer." Structure 27.1 (2019): 125-133.

Lau, Wai L., et al. "Using yeast surface display to engineer a soluble and crystallizable construct of hematopoietic progenitor kinase 1 (HPK1)." Acta Crystallographica Section F: Structural Biology Communications 77.1 (2021): 22-28.

Chuang, Huai-Chia, and Tse-Hua Tan. "MAP4K family kinases and DUSP family phosphatases in T-cell signaling and systemic lupus erythematosus." Cells 8.11 (2019): 1433.

Delpire, Eric. "The mammalian family of sterile 20p-like protein kinases." Pflügers Archiv-European Journal of Physiology 458 (2009): 953-967.

“Safety and Efficacy Study of CFI-402411 in Subjects with Advanced Solid Malignancies - Full Text View - ClinicalTrials.gov.” Clinicaltrials.gov, classic.clinicaltrials.gov/ct2/show/NCT04521413. Accessed 30 Sept. 2023.

Study of NDI 1150-101 in Patients with Solid Tumors. https://clinicaltrials.gov/ct2/show/NCT05128487?cond=HPK1&draw=1&rank=10 (accessed September 24, 2023).

A Phase I/II Study to Evaluate the Safety, Pharmacokinetics and Efficacy of PRJ1-3024 in Subjects with Advanced Solid Tumors. https://clinicaltrials.gov/ct2/show/NCT05315167?cond=HPK1&draw=1&rank=7 (accessed September 24, 2023)

BGB-15025 Alone and in Combination with Anti-PD-1 Monoclonal Antibody Tislelizumab in Participants with Advanced Solid Tumors. https://clinicaltrials.gov/ct2/show/NCT04649385 (accessed September 24, 2023)

PF-07265028 As Single Agent and In Combination with Sasanlimab in Advanced or Metastatic Solid Tumors. https://www.clinicaltrials.gov/ct2/show/NCT05233436?cond=HPK1&draw=2&rank=5 (accessed September 24, 2023)

A Phase I Study of RGT-264 in Subjects with Advanced Solid Tumors. https://www.clinicaltrials.gov/ct2/show/NCT05764915?term=HPK1&cond=HPK1&draw=2&rank=5 (accessed September 24, 2023)

UNIVERSITY HEALTH NETWORK. Compiler: WO2016205942A1[P]. 2016-12-29.

Toure, Momar, et al. "Discovery of quinazoline HPK1 inhibitors with high cellular potency." Bioorganic & Medicinal Chemistry 92 (2023): 117423.

Wang, Beilei, et al. "An overview of kinase downregulators and recent advances in discovery approaches." Signal Transduction and Targeted Therapy 6.1 (2021): 423.

" What is allosteric inhibitor? ". www.globecancer.com http://www.globecancer.com/azzx/show.php?itemid=14419#:~:text=%E5%88%AB%E6%9E%84%E6%8A%91%E5%88%B6%E5%89%82%E5%8F%88%E5%8F%AB%E5%8F%98 [Accessed 23 Sep. 2023].

Wang, Weixue, et al. "Discovery of an allosteric, inactive conformation-selective inhibitor of full-length HPK1 utilizing a kinase cascade assay." Biochemistry 60.41 (2021): 3114-3124..

Qi, Si-Min, et al. "PROTAC: an effective targeted protein degradation strategy for cancer therapy." Frontiers in Pharmacology 12 (2021): 692574.

" PROTACs and Molecular Glues. ". www.astrazeneca.com https://www.astrazeneca.com/r-d/next-generation-therapeutics/protacs.html.

" PROTAC Technology: tool for new therapies development. " https://www.drugtimes.cn/2021/08/28/xinyaoyanfaliqiprotacjishuzuiquanjiedu/

Si, Jingwen, et al. "Hematopoietic progenitor kinase1 (HPK1) mediates T cell dysfunction and is a druggable target for T cell-based immunotherapies." Cancer Cell 38.4 (2020): 551-566.

Dale, Brandon, et al. "Advancing targeted protein degradation for cancer therapy." Nature Reviews Cancer 21.10 (2021): 638-654.

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Published

29-12-2023

How to Cite

Yuan, Z., & Pan, Z. (2023). Hematopoietic Progenitor Kinase 1 Inhibitors. Highlights in Science, Engineering and Technology, 74, 1694-1703. https://doi.org/10.54097/kcpmqa71