1. Academic Validation
  2. CA-170 - A Potent Small-Molecule PD-L1 Inhibitor or Not?

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

  • Molecules. 2019 Aug 1;24(15):2804. doi: 10.3390/molecules24152804.
Bogdan Musielak 1 Justyna Kocik 1 Lukasz Skalniak 1 Katarzyna Magiera-Mularz 1 Dominik Sala 1 Miroslawa Czub 1 Malgorzata Stec 2 Maciej Siedlar 2 Tad A Holak 1 Jacek Plewka 3
Affiliations

Affiliations

  • 1 Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland.
  • 2 Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, Wielicka 265, 30-663 Krakow, Poland.
  • 3 Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland. jacek.plewka@uj.edu.pl.
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.

Keywords

CA-170; HTRF; NMR; PD-1/PD-L1; immune checkpoint.

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