Erschienen in:
Frontiers in Pharmacology, 13 (2022)
Sprache:
Nicht zu entscheiden
DOI:
10.3389/fphar.2022.850855
ISSN:
1663-9812
Entstehung:
Anmerkungen:
Beschreibung:
<jats:p>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<jats:sub>50</jats:sub> values below 20 μM, and the most potent one (compound M074-2865) had an IC<jats:sub>50</jats:sub> value of 2.93 ± 0.09 μM. 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.</jats:p>