Identification of Dinaciclib and Ganetespib as anti-inflammatory drugs using a novel HTP screening assay that targets IFNγ-dependent PD-L1.

ABSTRACT:

Introduction

IFNγ plays both positive and negative roles in the regulation of innate and adaptive immune responses against tumors and virally infected tissues by upregulating CXCL10 and PD-L1 expression.

Methods

To identify novel pathways and drugs that regulate the IFNγ-dependent PD-L1, we expressed GFP under the control of mouse PD-L1 promoter in mouse cancer cells that up regulate PD-L1 and CXCL10 in response to IFNγ stimulation. Using these cells, we screened an FDA approved library of 1496 small molecules known for their ability to inhibit IFNγ-dependent increase in PD-L1.

Results

We identified 46 drugs that up regulated and 4 that down regulated IFNγ-dependent PD-L1 expression. We discovered that in addition to the known JAK inhibitors Ruxolitinib and Baricitini

SUBMITTER: Hagbi-Levi S 

PROVIDER: S-EPMC12011776 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature