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bioRxiv · 10.1101/662668

CA-170 a potent small-molecule PD-L1 inhibitor or not?

Musielak, B.·Kocik, J.·Skalniak, L.·Magiera-Mularz, K.·Sala, D.·Czub, M.·Holak, T. A.·Plewka, J.
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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 p57.

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Musielak, B., Kocik, J., Skalniak, L., Magiera-Mularz, K., Sala, D., Czub, M., Holak, T. A., Plewka, J.. 2019-06-06. CA-170 a potent small-molecule PD-L1 inhibitor or not?. https://doi.org/10.1101/662668

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