Evaluation of STK17B as a cancer immunotherapy target utilizing highly potent and selective small molecule inhibitors.

ABSTRACT:

Introduction

The serine/threonine kinase 17B (STK17B) is involved in setting the threshold for T cell activation and its absence sensitizes T cells to suboptimal stimuli. Consequently, STK17B represents an attractive potential target for cancer immunotherapy.

Methods

To assess the potential of STK17B as an immuno-oncology target, we developed potent and selective tool compounds from starting points in Blueprint Medicines Corporation's proprietary kinase inhibitor library. To characterize these molecules, enzyme and cellular assays for STK17A and STK17B were established to drive chemistry optimization. Mass spectrometry-based phosphoproteomics profiling with tool inhibitors led to the identification of Ser19 on myosin light chain 2 as STK17B substrate, which is then developed

SUBMITTER: Scheuplein F 

PROVIDER: S-EPMC11536310 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature