Substance P (4-11): pain & nausea research fragment (Octa-Substance P)
A lab-made fragment of substance P, the body's natural pain-and-inflammation signal, used in research to study how pain and nausea signals work in the nervous system. Research tool only.
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
What this is
Substance P (4-11) — also called octa-substance P, or octa-(4-11)-SP — is the C-terminal eight-residue fragment of substance P, one of the best-studied neuropeptides in the body. Full substance P (RPKPQQFFGLM) is an 11-amino-acid signaling peptide released by nerve endings during pain, inflammation, and stress responses; the (4-11) fragment is its biologically active tail end, sequence PQQFFGLM. This shorter version retains the ability to activate the neurokinin-1 receptor (NK1R, also called TACR1) and has been widely used in laboratory research to map which parts of the substance P sequence drive receptor binding and biological effects. Active analogs studied in the literature carry a C-terminal amide (-NH₂) modification that is not represented in the raw stored sequence here.
History
The biological importance of substance P's C-terminal region was established in the mid-1970s. Bury and colleagues (Journal of Medicinal Chemistry, 1976) systematically tested shortened C-terminal fragments of substance P and showed that these partial sequences retain pharmacological activity. A companion study by Bury and colleagues (Clinical and Experimental Pharmacology and Physiology, 1977) characterized synthetic substance P on isolated guinea-pig ileum, demonstrating that its smooth-muscle-contracting effect is not mediated by cholinergic pathways. Couture and colleagues (Canadian Journal of Physiology and Pharmacology, 1979) then used octa-(4-11)-SP as a reference compound to probe the role of its phenylalanine residues, finding that replacing both phenylalanines with the bulkier carboranylalanine rendered the analogs practically inactive — establishing those two aromatic residues as essential for biological activity.
What it does
Substance P (4-11) binds the neurokinin-1 receptor (NK1R/TACR1), a G protein-coupled receptor that substance P and related tachykinin neuropeptides use to transmit signals related to pain, neurogenic inflammation, nausea, and vomiting. As Steinhoff and colleagues (Physiological Reviews, 2014) describe, the tachykinin family — of which substance P is the founding member — participates in physiological control across the nervous, immune, gastrointestinal, respiratory, and urogenital systems, signaling through three neurokinin receptor subtypes. The (4-11) octapeptide captures the receptor-activating core of the full molecule, making it useful for characterizing NK1R function in isolation from the N-terminal residues of the full peptide. Schank and colleagues (International Review of Neurobiology, 2017) note the NK1R/substance P axis as a key driver of stress-related neurobiology, with implications for nausea pathways and neurogenic inflammation.
Evidence
- Human: No human clinical trials for substance P (4-11) specifically. It is used as a laboratory research tool rather than a clinical compound.
- Animal: Pharmacological activity on guinea-pig ileum smooth muscle demonstrated by Bury and colleagues (1977). The spasmogenic effect was not blocked by atropine or hexamethonium, indicating a non-cholinergic, non-adrenergic mechanism.
- In vitro: Couture and colleagues (1979) showed that phenylalanine residues within the octa-(4-11)-SP sequence are essential for biological activity; replacing both Phe residues with carboranylalanine eliminated activity in binding assays. The fragment also appears as a C-terminal component in hybrid antimicrobial peptides characterized by Miao and colleagues (Biochimica et Biophysica Acta, 2020), illustrating continued use of this sequence as a functional building block.
Known effects
- NK1R/TACR1 agonism — Research tool; no clinical approval
- Smooth muscle contraction (gut) — Demonstrated in isolated guinea-pig ileum preparations (Bury and colleagues, 1977)
- Structural probe — Used to define the minimal pharmacophore of substance P at the neurokinin-1 receptor (Couture and colleagues, 1979)
Regulatory status
- US: Not approved by the FDA. Substance P (4-11) is a research reagent; it holds no IND, NDA, or approved indication.
- EU: Not approved by the EMA.
- WADA: Not listed on the current WADA prohibited list.
Related peptides
Substance P (4-11) is part of the broader tachykinin neuropeptide family. The full-length parent peptide is substance P (RPKPQQFFGLM), and related mammalian tachykinins include neurokinin A and neurokinin B, all of which share the C-terminal -FFXLM-NH₂ motif responsible for NK receptor activation (Steinhoff and colleagues, 2014). Galantide — a chimeric peptide in which galanin's N-terminal sequence is fused to the SP(5-11) C-terminal portion — uses an overlapping fragment as its receptor-activating element (as documented in the galanin receptor literature).
Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.
Could the two glutamine residues near the start of this peptide be responsible for folding it into the exact shape needed to activate its receptor?
If true, drug designers could replace these glutamines with artificial hinges that resist breakdown by body enzymes, creating longer-lasting pain or nausea medicines. This would help patients who need steady medication levels.
Could this short peptide trigger blood vessel contraction through a receptor different from the one it uses in the brain?
If true, doctors might one day use this peptide or its derivatives to help control blood flow in emergencies like severe bleeding or shock, or to treat migraines linked to abnormal vessel dilation. This could help patients in acute care settings.
Could this smaller fragment of substance P penetrate inflamed tissues more easily and influence immune cell behavior through the same receptor it uses in the nervous system?
If true, this peptide could lead to new anti-inflammatory treatments for conditions like arthritis or inflammatory bowel disease that are applied directly to affected areas. This would help patients who cannot tolerate systemic immune-suppressing drugs.
Could the spacing of two specific phenylalanine residues in this peptide determine whether it fully or only partially activates its target receptor?
If true, researchers could design new pain or nausea drugs that dial receptor activation up or down precisely, potentially reducing side effects like tolerance that come from over-activation. This would help patients needing chronic pain or chemotherapy-induced nausea relief.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.9572442173957825 | boltz-2 |
| ranking score | 0.7873091697692871 | boltz-2 |
▸3-letter notation
▸recipeboltz-2 2.2.1
| parameter | value |
|---|---|
| model | boltz-2 2.2.1 |
| weights | — |
| hardware | vast_v100_32gb |
| mlx version | — |
| python | — |
| random seed | 1 |
| msa strategy | colabfold_local |
| runtime | — |
| predicted by | — |
| predicted at | 2026-05-22 |
▸citationbibtex
@peptide{pep10626,
sequence = {PQQFFGLM},
target = {tacr1},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}