In Vitro Assessment of Putative PD-1/PD-L1 Inhibitors: Suggestions of an Alternative Mode of Action

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dc.contributor.authorBlevins, Derek J.
dc.contributor.authorHanley, Ronan
dc.contributor.authorBolduc, Trevor
dc.contributor.authorPowell, David A.
dc.contributor.authorGignac, Michael
dc.contributor.authorWalker, Kayleigh
dc.contributor.authorCarr, Mark D.
dc.contributor.authorHof, Fraser
dc.contributor.authorWulff, Jeremy E.
dc.date.accessioned2020-06-19T20:18:04Z
dc.date.copyright2019en_US
dc.date.issued2019
dc.description.abstractThe 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.en_US
dc.description.embargo2020-07-02
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipThis work was supported by funding from the Canadian Cancer Society Research Institute (grant # 701684), as well as an NSERC CREATE grant (# 497311–2017) and an NSERC Discovery grant to J.W. (# 4283). Additional support came from the Michael Smith Foundation for Health Research, the Canada Research Chairs program, and the University of Victoria.en_US
dc.identifier.citationBlevins, D. J., Hanley, R., Bolduc, T., Powell, D. A., Gignac, M., Walker, K., Carr, M. D., Hof, F., & Wulff, J. E. (2019). In vitro assessment of putative PD-1/PD-L1 inhibitors: Suggestions of an alternative mode of action. ACS Medicinal Chemistry Letters, 10(8), 1187-1192. https://doi.org/10.1021/acsmedchemlett.9b00221en_US
dc.identifier.urihttps://doi.org/10.1021/acsmedchemlett.9b00221
dc.identifier.urihttp://hdl.handle.net/1828/11864
dc.language.isoenen_US
dc.publisherACS Medicinal Chemistry Lettersen_US
dc.subjectPD-1
dc.subjectPD-L1
dc.subjectprotein-protein interaction inhibitors
dc.subjectSPR
dc.subject.departmentDepartment of Chemistry
dc.titleIn Vitro Assessment of Putative PD-1/PD-L1 Inhibitors: Suggestions of an Alternative Mode of Actionen_US
dc.typePostprinten_US

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