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For a quantitative insight, this finding was further confirmed by flow cytometry (flow cytometry plots: Fig

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Given the observed hydrogen-bonding interactions with Q726 and Y524 and considering the contribution of the P-clamp region to PDE10A selectivity, future optimization should prioritize (i) enhancing potency by incorporating structural constraints that properly orient key substituents to reinforce the Q726/Y524 hydrogen-bond network and (ii) modulating lipophilicity and polar surface area to achieve an optimal balance between CNS penetration and effective P-clamp engagement