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Substance P is the endogenous 11-residue tachykinin Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2. It is the preferred endogenous agonist of the neurokinin-1 receptor, NK1/TACR1, and serves as a reference ligand in tachykinin receptor pharmacology.
Its biological activity depends on both the amidated hydrophobic C-terminal pharmacophore and contributions from the N-terminal sequence. Substance P is widely used in NK1 signaling, receptor binding, neuronal and smooth-muscle studies, peptide metabolism, and structure–activity comparisons with truncated or modified analogs.
Product Information
| Product Name | Substance P |
| Catalog No. | AS2721 |
| CAS No. | 33507-63-0 |
| Sequence | Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 |
| One-Letter Sequence | RPKPQQFFGLM-NH2 |
| Peptide Length | 11 residues |
| Molecular Formula | C63H98N18O13S |
| Molecular Weight | Approximately 1347.6 Da |
| C-Terminus | Amidated |
| Primary Target | NK1 receptor / TACR1 |
| Pharmacological Profile | Endogenous full agonist |
Substance P Preferentially Activates NK1
Substance P is the preferred endogenous tachykinin ligand for NK1. Curated human receptor data report NK1 pKi values of approximately 8.5–10.3.
Affinity for NK2 and NK3 is substantially lower, although Substance P should not be described as absolutely receptor-specific at sufficiently high concentrations.
The Amidated C-Terminal Pharmacophore
The Phe-Phe-Gly-Leu-Met-NH2 sequence contributes strongly to tachykinin receptor recognition, while upstream residues enhance NK1 affinity and signaling.
Comparison with Substance P Free Acid demonstrates that C-terminal amidation is also a critical part of the active molecular structure.
Met11 Oxidation
Met11 can oxidize to methionine sulfoxide, producing a +16 Da mass shift. For quantitative signaling or receptor-binding experiments, we recommend monitoring peptide integrity when comparing old solutions, repeated freeze-thaw samples or different lots.
Research Applications
Substance P can support NK1 receptor pharmacology, second-messenger signaling, neuronal and smooth-muscle research, peptide metabolism and tachykinin SAR.
Custom Substance P analogs, non-natural amino acids and project-specific modifications are available through our Chemical Peptide Synthesis service.
Frequently Asked Questions
What is the sequence of Substance P?
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2.
What is its primary receptor?
NK1, also called TACR1.
Is Substance P completely selective for NK1?
No. It strongly prefers NK1 but can interact with other tachykinin receptors at higher concentrations.
Why is the C-terminal amide important?
Amidation is a critical structural feature of the active tachykinin pharmacophore.
Should Met11 oxidation be monitored?
Yes. Oxidation creates a +16 Da mass shift and can introduce chemical heterogeneity.