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

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.

SUBMITTER: Musielak B

PROVIDER: S-EPMC6695792 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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

Musielak Bogdan B Kocik Justyna J Skalniak Lukasz L Magiera-Mularz Katarzyna K Sala Dominik D Czub Miroslawa M Stec Malgorzata M Siedlar Maciej M Holak Tad A TA Plewka Jacek J

Molecules (Basel, Switzerland) 20190801 15

<b>CA-170</b> 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 method ...[more]

PMID: 31374878

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