Semax

Research · Semax

Overview

Semax is a synthetic seven-residue analog of the adrenocorticotropic hormone fragment ACTH(4-10), with the sequence Met-Glu-His-Phe-Pro-Gly-Pro. The native ACTH(4-7) segment is extended at the C-terminus by a Pro-Gly-Pro glyproline motif that confers resistance to proteolytic degradation. Developed at the Institute of Molecular Genetics of the Russian Academy of Sciences, it lacks the corticotropic (adrenal steroidogenic) activity of full-length ACTH and is studied as a reference compound in neurotrophic and cerebral ischemia research. Its compact structure and stability have made it a frequent comparator in studies of short regulatory sequences derived from melanocortin precursors.

Mechanism of action

The precise receptor target has not been fully defined; melanocortin receptor interaction has been proposed but remains unconfirmed. The best-characterized reported effect is upregulation of brain-derived neurotrophic factor (BDNF) and its receptor TrkB in rodent hippocampus and basal forebrain. Transcriptomic studies in ischemia models report modulation of genes linked to inflammation, vascular function, and neurotransmission. Additional proposed actions include inhibition of enkephalin-degrading enzymes and modulation of dopaminergic and serotonergic signaling. The C-terminal Pro-Gly-Pro motif slows N-terminal and C-terminal cleavage relative to native ACTH fragments. Reported downstream effects include altered expression of genes encoding neurotrophins, chemokines, and vascular regulators in ischemic rat cortex, consistent with a broad transcriptional rather than single-receptor mode of action.

Key research findings

1. 01

   Rodent studies document increased hippocampal BDNF and TrkB expression following administration, characterized at both transcript and protein levels.

2. 02

   Rat models of cerebral ischemia-reperfusion characterize altered brain gene and protein expression profiles associated with the compound.

3. 03

   Functional MRI studies in human volunteers have characterized changes in default mode network connectivity following administration.

4. 04

   Primary research is published in Russian-language journals and remains uncharacterized in Western clinical databases.

Published references

• Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus

  Dolotov OV et al. — Brain Res, 2006 · PMID: 16996037

• Effects of Semax on the Default Mode Network of the Brain

  Lebedeva IS et al. — Bull Exp Biol Med, 2018 · PMID: 30225715

The information above is derived from published preclinical and clinical research. It is provided for educational purposes only and does not constitute medical advice, diagnosis, or treatment recommendations.