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Critical limitations of this work: group sizes were small (roughly 10 animals per group, typical for exploratory metabolic studies of this type), the study was conducted in a single laboratory, the results have not been independently replicated in a separate published study, and the mouse model of diet-induced obesity does not faithfully recapitulate the genetic, hormonal, and behavioral complexity of human obesity
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This structural modification was rationally designed to optimize binding affinity to NNMT while dramatically improving membrane permeability — a critical limitation of the parent 1-MQ molecule
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