Set the two sequences side by side and the family resemblance is obvious:
Met-Glu-His-Phe-Pro-Gly-Pro
Thr-Lys-Pro-Arg-Pro-Gly-Pro
The bold half is identical. Everything before it is not, and that is where the comparison actually lives.
The shared half is a stability trick
Short peptides derived from hormone fragments are destroyed within minutes by aminopeptidases and carboxypeptidases. The proline-rich Pro-Gly-Pro tail markedly slows that, and a whole family of Russian peptide drugs is built on exactly this move.
Take a short native peptide with known central activity, bolt on the glyproline stabiliser
Pick a native fragment
ACTH(4-7) for Semax; tuftsin (Thr-Lys-Pro-Arg) for Selank
Add Pro-Gly-Pro
The proline-rich tail that slows aminopeptidase and carboxypeptidase attack
Result
Met-Glu-His-Phe-Pro-Gly-Pro and Thr-Lys-Pro-Arg-Pro-Gly-Pro, chemically unambitious by design
This explains why both compounds look chemically unambitious next to Western analogues. The goal was never receptor optimisation, it was to take something the body already makes and keep it intact long enough to matter.
The different halves are different pharmacology
Shared stabiliser, unrelated pharmacology
Semax
- Origin: ACTH(4-7), a fragment of a corticotropic hormone
- Premise: keeps behavioural activity, drops the endocrine one[1]
- Reported action: rapid induction of NGF and BDNF transcription, peaking at 30 minutes[1]
Selank
- Origin: tuftsin, released from the Fc portion of IgG
- Premise: an anxiolytic that avoids the GABA_A receptor entirely
- Reported action: inhibits enkephalin degradation, IC₅₀ around 15 μM[2]
Semax begins from ACTH(4-7). The premise, taken apart in the Semax article, is a dissociation: full ACTH drives cortisol release, while the 4-10 fragment retains behavioural and neurotropic activity without that endocrine action. The mechanistic anchor is transcriptional, NGF and BDNF mRNA rising in glial cells, fastest at 30 minutes1.
Selank begins from tuftsin, a fragment released from immunoglobulin G and known since the 1970s as a stimulator of phagocytosis. Its proposed mechanism, covered in the Selank article, is not receptor agonism at all: it inhibits the enzymatic hydrolysis of plasma enkephalin, dose-dependently, with an IC₅₀ around 15 μM2.
One is proposed to increase production of growth factors. The other is proposed to slow the destruction of the body's own opioid signalling. These are not variations on a theme.
The weakness they do share
Both carry the same evidentiary asymmetry, and it is the reason this library treats them cautiously.
The mechanistic work is specific and, within its own tradition, replicated. The clinical literature is narrow, largely produced by the groups that developed the compounds, and would not survive the scrutiny a Western regulatory programme applies. That is not an accusation of fraud, it is a description of how thin an evidence base is when it comes from one place.
There is a second, subtler problem specific to this pair. Pro-Gly-Pro is not inert. The ischaemia work found that both Semax and bare Pro-Gly-Pro activated neurotrophin and receptor transcription, on partly overlapping profiles4.
If the shared tail does something on its own, then attributing an effect to "Semax" rather than to the stabiliser requires a control that includes the tail alone, and much of the literature does not.
Choosing between them
For a research reagent the choice follows the question, not a ranking.
If the interest is neurotrophin transcription, the ACTH fragment and the ischaemia model work is the relevant literature. If the interest is peptidase inhibition and endogenous opioid tone, the tuftsin lineage is. Nothing in either body of work supports treating them as interchangeable, and nothing supports treating one as a stronger version of the other.
Both need the same handling. Both are heptapeptides of similar mass, 813.9 and 751.9 g/mol, and both behave in solution like any other short peptide, which is to say the arithmetic in the reconstitution piece applies unchanged.
And for both, the honest summary is the one their own literature supports: a specific proposed mechanism, a narrow evidence base, and no human data of the kind that would let anyone say what happens in a person.
