Article ; Online: The HPK1 Inhibitor A-745 Verifies the Potential of Modulating T Cell Kinase Signaling for Immunotherapy.
ACS chemical biology
2022 Volume 17, Issue 3, Page(s) 556–566
Abstract: Hematopoietic progenitor kinase 1 (HPK1) is an MAP4K family member within the Ste20-like serine/threonine branch of the kinome. HPK1 expression is limited to hematopoietic cells and has a predominant role as a negative regulator of T cell function. ... ...
Abstract | Hematopoietic progenitor kinase 1 (HPK1) is an MAP4K family member within the Ste20-like serine/threonine branch of the kinome. HPK1 expression is limited to hematopoietic cells and has a predominant role as a negative regulator of T cell function. Because of the central/dominant role in negatively regulating T cell function, HPK1 has long been in the center of interest as a potential pharmacological target for immune therapy. The development of a small molecule HPK1 inhibitor remains challenging because of the need for high specificity relative to other kinases, including additional MAP4K family members, that are required for efficient immune cell activation. Here, we report the identification of the selective and potent HPK1 chemical probe, A-745. In unbiased cellular kinase-binding assays, A-745 demonstrates an excellent cellular selectivity binding profile within pharmacologically relevant concentrations. This HPK1 selectivity translates to an |
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MeSH term(s) | Immunologic Factors ; Immunotherapy ; Protein Serine-Threonine Kinases ; Signal Transduction ; T-Lymphocytes |
Chemical Substances | Immunologic Factors ; hematopoietic progenitor kinase 1 (EC 2.7.1.11) ; Protein Serine-Threonine Kinases (EC 2.7.11.1) |
Language | English |
Publishing date | 2022-02-21 |
Publishing country | United States |
Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. |
ISSN | 1554-8937 |
ISSN (online) | 1554-8937 |
DOI | 10.1021/acschembio.1c00819 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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