Identification of ALPK1 inhibitors

National Center For Advancing Translational Sciences

Investigators

Abstract

The goal of the project during the reporting period has been to establish a high-throughput screening assay to assess phosphorylation by ALPK1 upon stimulation by its ligand ADP-heptose. The assay utilizes a commercially available HEK293 NF-kB reporter cell line expressing ALPK1. Candidate compounds will be evaluated for reporter activation in the presence or absence of ADP-heptose. Compounds will be subsequently evaluated for on target activity in the presence of TNF-alpha, which activates the NF-kB reporter independently of ALPK1. The assay is being screened against small molecule libraries and potential hits have been identified. A biochemical assay will be developed to confirm on target activity.