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HPK1 is a brake inside immune cells: it dampens a T cell's response once the cell has recognised its target. Blocking it is meant to let T cells attack a tumour harder, and an HPK1 inhibitor is in an early trial, alone and with a checkpoint antibody.
MAP4K1, better known as HPK1 (hematopoietic progenitor kinase 1, chromosome 19q13.2), is a serine/threonine kinase of the MAP4K family that acts upstream of the JUN N-terminal kinase pathway and may help regulate blood-cell lineage decisions (UniProt Q92918). Its expression is restricted to blood-forming cells. In mice, T cells lacking HPK1 made more Th1 cytokines after T-cell receptor engagement, proliferated faster, resisted suppression by prostaglandin E2, and protected recipients against lung tumour growth after adoptive transfer; dendritic cells lacking it presented antigen better (Immunologic Research 2012, doi:10.1007/s12026-012-8319-1). In OnCo, CFI-402411 is an oral HPK1 inhibitor tested alone and with pembrolizumab in advanced solid tumours.
In plain words · HPK1 is a brake inside immune cells: it dampens a T cell's response once the cell has recognised its target. Blocking it is meant to let T cells attack a tumour harder, and an HPK1 inhibitor is in an early trial, alone and with a checkpoint antibody.
HPK1 is a brake inside immune cells: it dampens a T cell's response once the cell has recognised its target. Blocking it is meant to let T cells attack a tumour harder, and an HPK1 inhibitor is in an early trial, alone and with a checkpoint antibody.
Hematopoietic cell-restricted MAP4K family serine/threonine kinase; a negative regulator of T-cell receptor signalling in the cited mouse studies, so inhibition is an immune-activating rather than a tumour-cell-killing strategy.
1 product aims at HPK1 (MAP4K1): small molecules. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
Hematopoietic cell-restricted MAP4K family serine/threonine kinase; a negative regulator of T-cell receptor signalling in the cited mouse studies, so inhibition is an immune-activating rather than a tumour-cell-killing strategy.
CFI-402411 is an experimental small molecule from Treadwell Therapeutics, in phase 1 trials for advanced solid tumours; its current status is not stated.
Query for this target: (TITLE:"HPK1" OR ABSTRACT:"HPK1" OR TITLE:"MAP4K1" OR ABSTRACT:"MAP4K1" OR TITLE:"hematopoietic progenitor kinase 1" OR ABSTRACT:"hematopoietic progenitor kinase 1" OR TITLE:"mitogen-activated protein kinase kinase kinase kinase 1" OR ABSTRACT:"mitogen-activated protein kinase kinase kinase kinase 1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about HPK1 (MAP4K1), not a curated reading list.
Shares Metastatic cancer (cancer that has spread) and the tag pipeline-gap-target.
Shares Metastatic cancer (cancer that has spread) and the tag pipeline-gap-target.
Shares Metastatic cancer (cancer that has spread) and the tag pipeline-gap-target.
Shares Metastatic cancer (cancer that has spread) and the tag pipeline-gap-target.
Shares CFI-402411, Metastatic cancer (cancer that has spread).
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