Discovery of ICOS-Targeted Small Molecules Using Affinity Selection Mass Spectrometry Screening.

ABSTRACT: Inducible T cell co-stimulator (ICOS) is a positive immune checkpoint receptor expressed on the surface of activated T cells, which could promote cell function after being stimulated with ICOS ligand (ICOS-L). Although clinical benefits have been reported in the ICOS modulation-based treatment for cancer and autoimmune disease, current modulators are restricted in biologics, whereas ICOS-targeted small molecules are lacking. To fill this gap, we performed an affinity selection mass spectrometry (ASMS) screening for ICOS binding using a library of 15,600 molecules. To the best of our knowledge, this is the first study that utilizes ASMS screening to discover small molecules targeting immune checkpoints. Compound 9 with a promising ICOS/ICOS-L inhibitory profile (IC₅₀=29.38±3.41 μ

SUBMITTER: Zhang L 

PROVIDER: S-EPMC11782461 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature