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. 2023 Dec 4;4:46. doi: 10.1186/s43556-023-00156-w

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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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 11 — Effects of allosteric modulators on receptor signaling. PAMs (a) and NAMs (b) modulate the effect of orthosteric agonists, while NALs (c) have no influence on receptor signaling mediated by orthosteric agonists. BAMs (d) potentiate signaling pathway a while inhibiting signaling pathway b of the receptor. The dose-dependence curves (below) display the effect of orthosteric agonists in the presence of allosteric modulations. The color saturation indicates the concentrations of allosteric modulators. OA: orthosteric agonist. e The binding sites of BAMs in receptors. SBI-553 (blue) binds to the pocket located at an intracellular region composed of TM6-7 and H8 of NTSR1 (PDB: 8FN0), while compound 9n sits in the upper portion between TM5-6 and ECL2 of HCAR2 (PDB: 8JII)