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Preparation of peptide derivatives as angiotensin IV receptor agonists

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(2015) described the development of angiotensin IV analogs including Dihexa and their HGF/c-Met potentiation mechanism (PMID: 25455861) Expression of Concern: The landmark 2012 paper describing Dihexa's cognitive effects received an expression of concern from the journal (PMID: 34551989), citing data integrity issues including questioned Western blot images Retraction: A follow-up paper from the same research group was retracted (PMID: 40312093), further undermining the evidence base for Dihexa's reported effects No Human Studies: No clinical trials, pharmacokinetic studies, or safety assessments have been conducted in humans Limited Independent Replication: The core claims about Dihexa's cognitive-enhancing effects have not been independently replicated by groups outside the original laboratory The Evidence Gap: This comparison starkly illustrates the difference between a compound with decades of clinical validation (Cerebrolysin) and one with provocative preclinical data undermined by integrity concerns (Dihexa)