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. 2023 Sep 25;8:364. doi: 10.1038/s41392-023-01625-y

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — The allosteric effect of compound 9n on HCAR2 downstream signaling induced by MK-6892. a The chemical structures of orthosteric agonists on HCAR2. b The allosteric effect of compound 9n on HCAR2 downstream signaling induced by MK-6892. The G_i protein signaling was determined by BRET-based G-protein dissociation assay (left panel) and β-arrestin1 recruitment was examined by NanoBiT assay (right panel). Dose-dependent curves were shown. Data are displayed as mean ± SEM from at least three independent experiments, each performed in triplicate. c Schematic presentation of the allosteric effect of compound 9n with the different orthosteric agonists at HCAR2. The figure created with BioRender.com