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Target intelligence / Profile preview
Hematopoietic Progenitor Kinase 1 (HPK1)
- Target
- HPK1
- Molecular classification
- Serine/threonine protein kinase, Ste20 family kinase
01
Overview
Hematopoietic Progenitor Kinase 1 (HPK1), also known as MAP4K1, is a serine/threonine kinase belonging to the Ste20 family. Primarily expressed in hematopoietic cells, HPK1 acts as a negative regulator of T cell, B cell, and dendritic cell signaling pathways. By phosphorylating key signaling molecules like SLP-76, HPK1 attenuates antigen receptor signaling and modulates immune responses. Loss or inhibition of HPK1 enhances immune cell activation and cytokine secretion, resulting in improved anti-tumor immunity. This makes HPK1 an attractive target for cancer immunotherapy, with several small-molecule inhibitors and PROTACs under clinical investigation.
- Other names
- MAP4K1Mitogen-activated protein kinase kinase kinase kinase 1
02
Mechanism of action
Small molecule inhibition of HPK1 kinase activity; PROTAC-mediated degradation of HPK1
03
Biological functions
Negative regulation of antigen receptor signalingModulation of immune responseRegulation of T cell receptor signalingRegulation of B cell receptor signalingApoptosis regulationMAPK signaling
04
Disease associations
CancerImmune dysregulation
05
Safety considerations
Potential for immune-related adverse events due to broad immune activation
06
Interacting drugs
NDI-101150
2 more in the full profile.
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