Cortagen

Cortagen (Ala-Glu-Asp-Pro; CAS 254749-42-7; molecular weight 414.41) is a four-residue synthetic peptide developed at the St. Petersburg Institute of Bioregulation and Gerontology by Vladimir Khavinson as a representative of the short-peptide bioregulator class derived from cortexin (a porcine cerebral cortex extract registered as a medicine in the Russian Federation). The Khavinson program isolated active fragments from organ-specific peptide extracts and characterized synthetic tetrapeptide and tripeptide analogs as the molecular basis of the parent extract's activity, including Cortagen for cerebral cortex, Pinealon (Glu-Asp-Arg) for pineal/CNS, Epitalon (Ala-Glu-Asp-Gly) for pineal, Vilon (Lys-Glu) for thymus, and several others. The proposed mechanism is direct DNA binding of the short peptides at promoter regions of tissue-specific genes, modulating transcription in a cell-type-restricted manner; published Russian-language work characterizes binding to specific GC-rich regulatory regions and effects on transcription factor recruitment. Pro-cognitive and neuroprotective activities of Cortagen are reported in rodent models of cerebral hypoxia, traumatic brain injury, and stress; Russian clinical reports describe efficacy in vegetative-vascular dystonia, post-traumatic asthenia, and discirculatory encephalopathy at intramuscular doses of 5 to 10 mg over 5 to 10 day courses. The Khavinson bioregulator class is registered as medicines in the Russian Federation and a small number of CIS jurisdictions; FDA, EMA, and most Western regulatory authorities have not reviewed the class. The principal limitation on the evidence base is the dominance of the originating laboratory's publications and the limited scale of clinical evidence relative to what would be required for Western regulatory approval. Investigators should weight the evidence accordingly.