Inducing Receptor Degradation as a Novel Approach to Target CC Chemokine Receptor 2 (CCR2).

ABSTRACT: CC chemokine receptor 2 (CCR2) has been linked to many inflammatory and immune diseases, making it a relevant drug target. Yet, all CCR2 antagonists developed so far have failed in clinical trials; thus, novel strategies are needed to target this receptor. Targeted protein degradation represents a novel approach to inhibit protein function by hijacking the cellular degradation machinery, such as the proteasome, to degrade the protein of interest. Here, we aimed to determine the amenability of CCR2 to chemically induced degradation by using a CCR2 fusion protein containing a HaloTag7 and HiBiT tag (CCR2-HaloTag-HiBiT). After characterization of the CCR2 construct, we used luminescence-based assays and immunofluorescence to quantify CCR2 levels, as well as a label-free, phenotypic assay to i

SUBMITTER: Ortiz Zacarias NV 

PROVIDER: S-EPMC11354370 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature