Huizhen Ge: College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, China.
Lizeng Peng: Institute of Agro-Food Science and Technology Shandong Academy of Agricultural Sciences, Key Laboratory of Agro-Products Processing Technology of Shandong Province, Key Laboratory of Novel Food Resources Processing Ministry of Agriculture, Jinan, China.
Zhou Sun: Academy of Advanced Interdisciplinary Studies, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China.
Huanxiang Liu: School of Pharmacy, Lanzhou University, Lanzhou, China.
Yulin Shen: Gansu Computing Center, Lanzhou, China.
Xiaojun Yao: College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, China.
Hematopoietic progenitor kinase (HPK1) is a negative regulator of T-cell receptor and B-cell signaling, which has been recognized as a novel antitumor target for immunotherapy. In this work, Glide docking-based virtual screening and kinase inhibition assay were performed to identify novel HPK1 inhibitors. The kinase inhibition assay results demonstrated five compounds with IC values below 20 ��M, and the most potent one (compound M074-2865) had an IC value of 2.93 �� 0.09 ��M. Molecular dynamics (MD) simulations were performed to delve into the interaction of sunitinib and the identified compound M074-2865 with the kinase domain of HPK1. The five compounds identified in this work could be considered promising hit compounds for further development of HPK1 inhibitors for immunotherapy.
