CA-170 - A Potent Small-Molecule PD-L1 Inhibitor or Not?

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Bogdan MusielakJacek Plewka

Abstract

CA-170 is currently the only small-molecule modulator in clinical trials targeting PD-L1 and VISTA proteins - important negative checkpoint regulators of immune activation. The reported therapeutic results to some extent mimic those of FDA-approved monoclonal antibodies overcoming the limitations of the high production costs and adverse effects of the latter. However, no conclusive biophysical evidence proving the binding to hPD-L1 has ever been presented. Using well-known in vitro methods: NMR binding assay, HTRF and cell-based activation assays, we clearly show that there is no direct binding between CA-170 and PD-L1. To strengthen our reasoning, we performed control experiments on AUNP-12 - a 29-mer peptide, which is a precursor of CA-170. Positive controls consisted of the well-documented small-molecule PD-L1 inhibitors: BMS-1166 and peptide-57.

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Datasets Mentioned

BETA
BMS-1166

Methods Mentioned

BETA
NMR
Assay
FRET
flow cytometry
AlphaScreen
gel filtration
electrophoresis

Clinical Trials Mentioned

NCT02812875

Software Mentioned

Mathematica
Aurigene

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