Discovery of an Allosteric, Inactive Conformation-Selective Inhibitor of Full-Length HPK1 Utilizing a Kinase Cascade Assay.
Sign Up to like & getrecommendations! Published in 2021 at "Biochemistry"
DOI: 10.1021/acs.biochem.1c00486
Abstract: Achieving selectivity across the human kinome is a major hurdle in kinase inhibitor drug discovery. Assays using active, phosphorylated protein kinases bias hits toward poorly selective inhibitors that bind within the highly conserved adenosine triphosphate… read more here.
Keywords: inhibitor; kinase; discovery; cascade assay ... See more keywords
Discovery of PF-07265028, A Selective Small Molecule Inhibitor of Hematopoietic Progenitor Kinase 1 (HPK1) for the Treatment of Cancer.
Sign Up to like & getrecommendations! Published in 2024 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.4c01930
Abstract: Hematopoietic progenitor kinase 1 (HPK1/MAP4K1) represents a high interest target for the treatment of cancer through an immune-mediated mechanism. Herein we present highlights of the drug discovery campaign within the lactam/azalactam series of inhibitors that… read more here.
Keywords: hematopoietic progenitor; hpk1; small molecule; kinase ... See more keywords
Discovery of a New and Selective HPK1 PROTAC for Enhancing Tumor Immunotherapy through Eliminating GLK Degradation.
Sign Up to like & getrecommendations! Published in 2025 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.4c02972
Abstract: HPK1 is an attractive therapeutic target for tumor immunotherapy. Nevertheless, the formidable challenge selectivity over GLK and limited antitumor efficacy of HPK1 inhibitors and PROTACs impeded their developments. Here, we demonstrated that blocking GLK alone… read more here.
Keywords: selective hpk1; tumor immunotherapy; hpk1; glk ... See more keywords
The HPK1 Inhibitor A-745 Verifies the Potential of Modulating T Cell Kinase Signaling for Immunotherapy.
Sign Up to like & getrecommendations! Published in 2022 at "ACS chemical biology"
DOI: 10.1021/acschembio.1c00819
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… read more here.
Keywords: hpk1 inhibitor; cell; 745 verifies; inhibitor 745 ... See more keywords
Discovery of Spiro-azaindoline Inhibitors of Hematopoietic Progenitor Kinase 1 (HPK1).
Sign Up to like & getrecommendations! Published in 2022 at "ACS medicinal chemistry letters"
DOI: 10.1021/acsmedchemlett.1c00473
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… read more here.
Keywords: spiro azaindoline; progenitor kinase; hpk1; kinase ... See more keywords
Abstract 463: GRC 54276, a novel small molecule inhibitor of HPK1 has entered phase 1/2 clinical trial insolid malignancies and Hodgkin’s/non Hodgkin’s lymphoma
Sign Up to like & getrecommendations! Published in 2023 at "Cancer Research"
DOI: 10.1158/1538-7445.am2023-463
Abstract: Background: Pre-clinical profile of GRC 54276, a clinical candidate with Phase 1/2 clinical trial ongoing, is presented here. GRC 54276 is a novel small molecule inhibitor of Hematopoietic progenitor kinase 1 (HPK1), a serine/threonine kinase1,2… read more here.
Keywords: 54276 novel; grc; hpk1; clinical trial ... See more keywords
Abstract 5014: HPK1 gene knockout reporter cell line: an efficient drug screening system
Sign Up to like & getrecommendations! Published in 2023 at "Cancer Research"
DOI: 10.1158/1538-7445.am2023-5014
Abstract: Immunotherapy is the stimulation of the immune system, improving on the ability of immune system to treat cancer. It is expected to be the most effective therapy for patients with tumor metastasis. Checkpoint inhibitor (CPI)… read more here.
Keywords: system; cell; reporter; cell line ... See more keywords
Abstract LB324: BB3008, a potent and selective small molecular HPK1 inhibitor effective in multiple syngeneic tumor models
Sign Up to like & getrecommendations! Published in 2023 at "Cancer Research"
DOI: 10.1158/1538-7445.am2023-lb324
Abstract: Introduction: Hematopoietic progenitor kinase 1 (HPK1) is a serine/threonine kinase in the MAP4K family predominantly expressed in immune cells, and has been identified as a negative regulator of T cell and B cell receptor signaling… read more here.
Keywords: hpk1 inhibitor; cell; tumor models; bb3008 ... See more keywords
Abstract 2654: HPK1 inhibits CD8+ T cell effector gene expression following T cell activation
Sign Up to like & getrecommendations! Published in 2024 at "Cancer Research"
DOI: 10.1158/1538-7445.am2024-2654
Abstract: Hematopoietic progenitor kinase 1 (HPK1) has been shown to act as a negative regulator of T cell receptor signaling and of subsequent effector T cell function. Inhibiting HPK1 to enhance T cell activity has emerged… read more here.
Keywords: cell activation; effector; cell; hpk1 ... See more keywords
Abstract 603: BB5523, a multiple kinase inhibitor with HPK1, VEGFR2 and TNIK inhibition, enhanced antitumor immunity in tumor models
Sign Up to like & getrecommendations! Published in 2024 at "Cancer Research"
DOI: 10.1158/1538-7445.am2024-603
Abstract: Introduction: Immuno-suppressive micro-environment and abnormal signaling pathways are crucial for the proliferation of tumor cells. Hematopoietic progenitor kinase 1 (HPK1) inhibitor plays important roles in activation of exhausted T cells and enhancement of anti-tumor immune… read more here.
Keywords: cancer; inhibition; kinase; tumor ... See more keywords
Abstract 7009: Discovery of UBX-306 as a potent, selective, and orally bioavailable HPK1 degrader
Sign Up to like & getrecommendations! Published in 2025 at "Cancer Research"
DOI: 10.1158/1538-7445.am2025-7009
Abstract: Hematopoietic progenitor kinase 1 (HPK1), part of the MAP4K family, is a serine/threonine kinase critical for modulating immune cell signaling and function. HPK1 is predominantly expressed in hematopoietic cells, where it acts as a negative… read more here.
Keywords: degradation; ubx 306; hpk1 degrader; cell ... See more keywords