Identity a synthetic heptapeptide (7 amino acids, < 40 aa → peptide) — the ACTH(4-7) active fragment (Met-Glu-His-Phe) with a C-terminal Pro-Gly-Pro extension added for metabolic stability. Developed at the Institute of Molecular Genetics, Russian Academy of Sciences (1980s). Crucially, despite being ACTH-derived, the (4-7/4-10) fragment does not stimulate cortisol/adrenal steroidogenesis (that requires ACTH 1-24). ## Development & history - Semax was engineered in the 1980s at the Institute of Molecular Genetics, Russian Academy of Sciences, out of a Soviet programme studying ACTH fragments for cognition and neuroprotection. Adding the Pro-Gly-Pro tail to the ACTH(4-7) fragment both stabilised the molecule and stripped its hormonal (cortisol-releasing) activity.
- It was registered as a drug in Russia in 1994, first for cerebrovascular disease (ischemic stroke), with cognitive and optic-nerve indications added later. It remains a Russia/CIS-approved medicine and is now under US compounding review (July 2026). ## Mechanism (as proposed) Semax is proposed to upregulate BDNF and NGF (with increased TrkB signalling), modulate dopamine/serotonin/acetylcholine systems, and provide neuroprotection during ischemia and against oxidative/neuroinflammatory injury — while, unlike parent ACTH, not triggering cortisol release. Much of the mechanistic detail is from animal work; the stroke-recovery use is better substantiated than the healthy-cognition use.