ArticleACS medicinal chemistry letters2022
Discovery of Spiro-azaindoline Inhibitors of Hematopoietic Progenitor Kinase 1 (HPK1).
Article in ACS medicinal chemistry letters, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 42 citations in OpenAlex.
- From inhibition to degradation: advances in highly selective targeting strategies for HPK1.Molecular diversity · 2026Review
- Enhancing kinase-inhibitor activity and selectivity prediction through contrastive learning.Nature communications · 2025Article
- Highly selective HPK1 inhibitor NDI-101150 mediates immune cell activation and robust antitumor responses, distinct from immune checkpoint blockade.Journal for immunotherapy of cancer · 2025Article
- Identification of Novel HPK1 Hit Inhibitors: From In Silico Design to In Vitro Validation.International journal of molecular sciences · 2025Article
- Design, Synthesis, and Biological Evaluation of a Series of Spiro Analogues as Novel HPK1 Inhibitors.ACS medicinal chemistry letters · 2024Article
- Discovery of GNE-6893, a Potent, Selective, Orally Bioavailable Small Molecule Inhibitor of HPK1.ACS medicinal chemistry letters · 2024Article
- HPK1 citron homology domain regulates phosphorylation of SLP76 and modulates kinase domain interaction dynamics.Nature communications · 2024Article
- Early Stage Preclinical Formulation Strategies to Alter the Pharmacokinetic Profile of Two Small Molecule Therapeutics.Pharmaceuticals (Basel, Switzerland) · 2024Article
- An updated review of small-molecule HPK1 kinase inhibitors (2016-present).Future medicinal chemistry · 2024Review
- Modular, automated synthesis of spirocyclic tetrahydronaphthyridines from primary alkylamines.Communications chemistry · 2023Article
- Potent and Selective Biaryl Amide Inhibitors of Hematopoietic Progenitor Kinase 1 (HPK1).ACS medicinal chemistry letters · 2023Article
- Discovery of Pyrazolopyridine Derivatives as HPK1 Inhibitors.ACS medicinal chemistry letters · 2023Article
- Multicomponent Direct Assembly ofThe Journal of organic chemistry · 2022Article
Corrections and comments
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Authors and funding
27 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hematopoietic progenitor kinase 1 (HPK1) is implicated as a negative regulator of T-cell receptor-induced T-cell activation. Studies using HPK1 kinase-dead knock-in animals have demonstrated the loss of HPK1 kinase activity resulted in an increase in T-cell function and tumor growth inhibition in glioma models. Herein, we describe the discovery of a series of small molecule inhibitors of HPK1. Using a structure-based drug design approach, the kinase selectivity of the molecules was significantly improved by inducing and stabilizing an unusual P-loop folded binding mode. The metabolic liabilities of the initial 7-azaindole high-throughput screening hit were mitigated by addressing a key metabolic soft spot along with physicochemical property-based optimization. The resulting spiro-azaindoline HPK1 inhibitors demonstrated improved
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.