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This partial agonism is intrinsic to orforglipron's binding mode: as an allosteric agonist occupying a smaller binding pocket with fewer receptor contacts than peptide ligands, it stabilizes a receptor conformation that is somewhat less efficient at coupling to Gs proteins than the fully peptide-activated state

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Indeed, we did find that HK-2 cells adhere tighter to the culture plate after a period of time of bismuth treatment, and the cells are harder to be detached by trypsin