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Since polyphenols can act as PAINS in biochemical assays (autofluorescence, redox cycling, aggregation, metal chelation), in-vitro hits without orthogonal validation were downgraded

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Both share the same core heptapeptide sequence, but Melanotan II has a cyclic structure via a lactam bond between Asp and Lys residues, while PT-141 is the open-chain form with a free N-terminal carboxylic acid group