Pain-signaling blocker (CHEMBL387670)
A lab-made peptide that blocks the nerve receptor for substance P, a chemical that carries pain and nausea signals; experimental, not an approved drug.
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
CHEMBL387670 is a short synthetic peptide designed in the laboratory as a research tool for blocking the neurokinin-1 receptor (NK1R, also called TACR1) — the main receptor for substance P, a neuropeptide involved in pain signaling, nausea, and neurogenic inflammation. It was engineered as part of a dual-action series aimed at producing compounds that could simultaneously silence NK1R and activate opioid receptors, with the goal of developing better analgesics. The compound has never been tested in humans and remains a research-stage molecule.
The raw five-letter sequence stored for this entry (YGFPL) is a simplified representation. The actual compound described in the source literature is an eight-residue molecule with several non-standard features that are not visible in the stored sequence: a D-amino acid at position 2 (D-Ala, encoded as standard A), an N-methylnorleucine residue at position 5, and a tryptophan residue capped with a 3,5-bis(trifluoromethyl)benzyl ester at the C-terminus. These modifications are integral to the compound's binding activity and are what distinguishes it from naturally occurring peptides.
What it does
CHEMBL387670 blocks the NK1/TACR1 receptor, the same receptor targeted by the FDA-approved antiemetic drugs aprepitant and netupitant. Blocking this receptor suppresses substance P signaling, which is involved in transmitting pain signals in the spinal cord, triggering nausea and vomiting, and amplifying neurogenic inflammation. In parallel, the opioid-agonist portion of the same molecule activates delta and mu opioid receptors, which are the targets of morphine-class analgesics.
The rationale behind this dual design is that NK1R signaling is known to contribute to the development of opioid tolerance: when opioid receptors and NK1R are simultaneously active during pain, the NK1 axis appears to blunt the analgesic effect over time. A single molecule that activates opioid receptors while blocking NK1R simultaneously could, in principle, provide analgesia while reducing the tolerance liability. This strategy was the research motivation behind the entire compound class to which CHEMBL387670 belongs.
Mechanism
CHEMBL387670 acts as an NK1 receptor antagonist with a binding affinity (Ki) of 0.71 nM at the rat NK1 receptor, measured by radioligand displacement assay (Yamamoto and colleagues, Journal of Medicinal Chemistry, 2007). It also displays affinity for delta and mu opioid receptors (δ Ki = 77 nM; μ Ki = 140 nM), consistent with the enkephalin-derived Tyr-D-Ala-Gly-Phe N-terminal pharmacophore shared across the compound series.
The molecule is built from two overlapping pharmacophore elements: an enkephalin-based tetrapeptide at the N-terminus that engages opioid receptors, and a substance P-antagonist segment at the C-terminus (anchored by the Pro-Leu-Trp-3,5-Bzl(CF3)₂ unit) that occupies the NK1 binding site. The fifth residue — N-methylnorleucine in this compound — sits at the interface between both recognition elements and serves as a structural address moiety that tunes both activities simultaneously. Methylation at the nitrogen of position 5 shifts the balance: NK1 affinity is preserved at sub-nanomolar levels while opioid affinity is somewhat reduced relative to companion compounds in the same series (Yamamoto and colleagues, 2007).
Evidence
- Human: No human data. CHEMBL387670 is a research compound that has not entered clinical development.
- Animal: Not reported individually for this compound. The broader bifunctional series to which it belongs was evaluated in rat models of nociception, where related compounds (TY005, TY027) demonstrated antinociceptive and antiallodynic activity (Yamamoto and colleagues, 2007; subsequent work by the same group).
- In vitro: Radioligand binding assays in rat brain membranes (NK1) and cell membranes expressing delta and mu opioid receptors; Ki = 0.71 nM at NK1 receptor (Yamamoto and colleagues, Journal of Medicinal Chemistry, 2007).
Regulatory status
- US: Not approved. Research compound only; no IND or clinical trial registration on record.
- EU: Not approved.
- WADA: No specific listing. Opioid receptor agonists as a class fall under S7 (Narcotics) on the WADA prohibited list; the NK1 antagonist activity of this compound is not separately scheduled.
▸full evidence table1 metrics
| metric | value | tool |
|---|---|---|
| Ki | 0.71 nM | GPCRDB/ChEMBL |
▸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{pep10455,
sequence = {YGFPL},
target = {tacr1},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}