Discovery of hematopoietic progenitor kinase 1 inhibitors using machine learning-based screening and free energy perturbation

Hematopoietic progenitor kinase 1 (HPK1) is a key negative regulator of T-cell receptor (TCR) signaling and a promising target for cancer immunotherapy. The development of novel HPK1 inhibitors is challenging yet promising. In this study, we used a combination of machine learning (ML)-based virtual...

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Bibliographic Details
Published in:Journal of biomolecular structure & dynamics 2024-01, p.1-13
Main Authors: Feng, Dazhi, Liu, Bo, Chen, Zhiwei, Xu, Jinyi, Geng, Meiyu, Duan, Wenhu, Ai, Jing, Zhang, Hefeng
Format: Article
Language:English
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Summary:Hematopoietic progenitor kinase 1 (HPK1) is a key negative regulator of T-cell receptor (TCR) signaling and a promising target for cancer immunotherapy. The development of novel HPK1 inhibitors is challenging yet promising. In this study, we used a combination of machine learning (ML)-based virtual screening and free energy perturbation (FEP) calculations to identify novel HPK1 inhibitors. ML-based screening yielded 10 potent HPK1 inhibitors (IC  
ISSN:0739-1102
1538-0254
DOI:10.1080/07391102.2024.2301754