Brian M Lacey, Zangwei Xu, Xiaomei Chai, Jason Laskey, Xavier Fradera, Payal Mittal, Sasmita Mishra, Jennifer Piesvaux, Peter Saradjian, Lynsey Shaffer, Galya Vassileva, Catherine Gerdt, Yun Wang, Heidi Ferguson, Dustin M Smith, Jeanine Ballard, Steven Wells, Rishabh Jain, Uwe Mueller, George Addona, Ilona Kariv, Joey L Methot, Mark Bittinger, Sheila Ranganath, Robbie Mcleod, Alexander Pasternak, J Richard Miller, Haiyan Xu
Hematopoietic progenitor kinase 1 (HPK1), also referred to as mitogen-activated protein kinase kinase kinase kinase 1 (MAP4K1), is a serine/threonine kinase that negatively regulates T-cell signaling by phosphorylating Ser376 of Src homology 2 (SH2) domain-containing leukocyte protein of 76 kDa (SLP-76), a critical mediator of T-cell receptor activation. HPK1 loss of function mouse models demonstrated enhanced immune cell activation and beneficial antitumor activity. To enable discovery and functional characterization of high-affinity small-molecule HPK1 inhibitors, we have established high-throughput biochemical, cell-based, and novel pharmacodynamic (PD) assays...
January 2021: SLAS Discovery