In Vitro Assessment of Putative PD-1/PD-L1 Inhibitors: Suggestions of an Alternative Mode of Action.
ACS Med Chem Lett
; 10(8): 1187-1192, 2019 Aug 08.
Article
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| MEDLINE
| ID: mdl-31413804
ABSTRACT
The programmed cell death protein 1 (PD-1) signaling axis is among the most important therapeutic targets in modern oncology. Aurigene Discovery Technologies Ltd. (Aurigene) has patented a series of peptidomimetic small molecules derived from the PD-1 protein sequence for use in targeting the interaction between PD-1 and its ligand, PD-L1. We evaluated three of Aurigene's most potent compounds in SPR binding assays. Our results showed that these compounds-each of which is known to be potently effective in a splenocyte recovery assay-do not directly inhibit the PD-1/PD-L1 interaction nor do they appear to bind to either of the constituent proteins, indicating that another mechanism is at play. As a result of these studies and upon consideration of structural features within the PD-1/PD-L1 complex, we hypothesize that the Aurigene molecules may interact with a currently unknown protein capable of regulating the PD-1 axis.
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1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
ACS Med Chem Lett
Año:
2019
Tipo del documento:
Article
País de afiliación:
Canadá