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In summary, both direct design relying on mechanistic knowledge and available structural data from the oxytocinase subfamily of M1 aminopeptidases as well as iterative manipulations of the parent peptide Ang IV, involving insertion of unnatural amino acids as -amino acids, macrocyclizations and various structural simplifications have provided highly potent selective Ang IV peptidemimetics inhibiting IRAP

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The phase 3 REDEFINE program, published in The New England Journal of Medicine and presented at the American Diabetes Associations Scientific Sessions in June 2025, put the combination to the test