A Potential Off-Target Effect of the Wnt/β-Catenin Inhibitor KYA1797K: PD-L1 Binding and Checkpoint Inhibition.

ABSTRACT:

Introduction

The quest for small molecule inhibitors of the PD-1/PD-L1 checkpoint continues in parallel to the extensive development of monoclonal antibodies directed against this immune checkpoint. Drug screening strategies are being set up to identify novel PD-L1 inhibitors.

Methods

A virtual screening based on molecular docking with the PD-L1 protein dimer has been performed to identify a new binder. Binding of the identified ligand to PD-L1 has been validated experimentally using a microscale thermophoresis (MST) assay. The cellular effect of the compound was evidenced using a fluorescence resonance energy transfer (FRET) assay based on activation of tyrosine phosphatase SHP-2.

Results

We have identified the potent Wnt/β-catenin inhibitor KYA1797K as a weak

SUBMITTER: Thuru X 

PROVIDER: S-EPMC10015704 | biostudies-literature | 2023 Jan-Dec

REPOSITORIES: biostudies-literature