[Pyr6,Pro9]-Substance P (6-11), commonly known as Septide, is a six-residue Substance P analog with an N-terminal pyroglutamate and Pro at position 9.

Septide is a well-established NK1 receptor agonist with unusual pharmacological behavior: it can produce strong functional NK1 responses despite showing substantially weaker competition than Substance P in some classical radioligand-binding assays.

Product Information

A Compact Substance P C-Terminal Agonist

Septide contains only residues corresponding to the C-terminal region of Substance P but retains strong NK1 agonist activity. Pyroglutamate caps the N-terminus of the fragment, while Pro9 replaces the native Gly residue.

The Pro9 substitution restricts local backbone conformation and was historically important in generating selectivity toward the Substance P-preferring receptor system now classified as NK1.

Functional Activity Can Differ from Binding Affinity

Septide became an important pharmacological tool because its functional potency was stronger than expected from some Substance P competition-binding experiments.

In recombinant rat NK1 receptors, both Substance P and septide produced similar maximal stimulation of inositol phosphate signaling. Reported EC₅₀ values in that system were approximately 0.05 nM for Substance P and 5 nM for septide.

This unusual relationship between binding and functional behavior led to extensive investigation of a historical “septide-sensitive” NK1 receptor state or binding mode.

We consider this feature more informative than simply describing septide as another NK1 agonist. It makes the peptide useful for experiments examining how ligand structure changes receptor activation and downstream signaling.

Research Applications

Septide can support NK1 receptor activation studies, tachykinin receptor differentiation, GPCR signaling experiments, smooth-muscle pharmacology and investigations of ligand-dependent NK1 receptor behavior.

Frequently Asked Questions

What is Septide?

Septide is the common name for [Pyr6,Pro9]-Substance P (6-11).

Is Septide an NK1 agonist?

Yes. It is a well-established NK1 receptor agonist.

Why is Septide pharmacologically interesting?

It can generate strong NK1 functional responses even when its apparent affinity in some Substance P competition-binding assays is lower than expected.

What does Pyr6 mean?

Pyr refers to pyroglutamate, also written pGlu, at the N-terminus of the six-residue peptide.

Does Septide contain methionine?

Yes. The peptide terminates in Met-NH₂.

Research Use Only.