CA-170 - A Potent Small-Molecule PD-L1 Inhibitor or Not?
Molecules
; 24(15)2019 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-31374878
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Bibliotecas de Moléculas Pequenas
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Antígeno B7-H1
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Imunoterapia
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Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article