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The L subunit, being relatively distant from the active site (25 ), does not obstruct ligand entry and is considered not to affect the binding of ligands to the dicopper center 60

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To address clinical and biological heterogeneity more directly, adaptive trial designs have gained prominence

The receptor is in an inactive conformation with compounds that restrict movement of the intracellular tip of helix VI, a movement that is generally associated with activation mechanisms in class A GPCRs 4,5,6

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