Semax 4-7

Semax 4-7 is the core tetrapeptide sequence Met-Glu-His-Phe, corresponding to ACTH amino acids 4–7. It represents the minimal active fragment underlying the nootropic and neuroprotective properties of Semax (ACTH(4-7)-Pro-Gly-Pro). Unlike full Semax, it lacks the C-terminal Pro-Gly-Pro extension that improves stability, resulting in a shorter-acting but more simplified pharmacological tool for studying ACTH-derived cognitive effects.

ACTH(4-7) interacts with melanocortin receptors (particularly MC4R in the brain) and modulates BDNF signaling, dopaminergic and serotonergic neurotransmission. Research suggests this tetrapeptide sequence is responsible for attention-enhancing and memory-consolidating effects attributed to ACTH analogs. It may enhance synaptic plasticity by upregulating neurotrophin expression. The Pro-Gly-Pro C-terminal extension in standard Semax primarily confers metabolic stability rather than adding distinct pharmacological activity.

Semax 4-7 research is largely foundational to understanding the active pharmacophore of Semax. Soviet and Russian research established that ACTH(4-7) fragments modulate learning and memory in rodent models. The full Semax molecule (with C-terminal Pro-Gly-Pro) has been more extensively studied and approved in Russia for stroke and cognitive impairment, with the 4-7 core considered the pharmacologically active portion. Limited standalone human data exist for the isolated tetrapeptide.

Peptides commonly paired with Semax 4-7 for synergistic effects.