NERP-1: nerve and hormone tissue peptide fragment
A small protein fragment from nerve and hormone tissue that switches on the calcitonin receptor, a signal involved in bone, heart, and metabolism. Used only as a lab research tool.
- Class
- Endogenous neuropeptide fragment
- Status
- No approved therapeutic status identified
- Best-supported effect
- Identified as an endogenous neuroendocrine peptide fragment in human tissue; no functional or therapeutic effect established
- Main caveat
- Biological activity has not been characterized in the compiled source; the single attached reference describes peptidomic identification 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
CGRP I precursor [107–119] is a 13-amino-acid peptide fragment cut from the precursor protein that the body uses to make calcitonin gene-related peptide (CGRP). Identified by Yamaguchi and colleagues (2007) in a peptidomic screen of neuroendocrine tissues, this fragment — also called Neuroendocrine Regulatory Peptide-1 (NERP-1) — is one of several biologically active pieces found embedded in the CGRP I precursor beyond the mature CGRP hormone itself. It targets the calcitonin receptor (CTR), a class B G protein-coupled receptor that sits at the center of a peptide hormone network spanning bone metabolism, cardiovascular tone, and metabolic regulation.
History
The CGRP I precursor encodes not only the 37-residue CGRP hormone but also flanking sequences that were long assumed to be inert processing byproducts. That assumption was overturned when Yamaguchi and colleagues (2007) used peptidomic mass spectrometry to identify NERP-1 (residues 107–119, sequence NNFVPTNVGSKAF) and NERP-2 as discrete, biologically validated peptides released from the precursor in neuroendocrine tissues. The calcitonin receptor itself has a well-documented history in bone biology: it was characterized as the primary mediator of calcitonin's inhibitory effect on osteoclast-driven bone resorption (Pondel 2000). Interest in CTR pharmacology has expanded substantially since the discovery that the receptor forms amylin receptors (AMY1–3) when it dimerizes with receptor activity-modifying proteins (RAMPs) 1, 2, or 3 — a structural insight reviewed comprehensively by Hay and colleagues (2018) in the IUPHAR pharmacology update on the calcitonin/CGRP peptide family.
What it does
CGRP I precursor [107–119] binds the calcitonin receptor and the related amylin receptor complexes formed when CTR partners with RAMPs. In bone, CTR activation on osteoclasts causes those bone-resorbing cells to retract from bone surfaces, reducing resorption (Pondel 2000). The expression of CTR is itself regulated during osteoclast maturation: Granholm and colleagues (2008) showed that RANKL — the key osteoclast-differentiating signal — progressively upregulates CTR mRNA in maturing osteoclasts, making CTR a marker of functional osteoclast identity. Beyond bone, CTR and its RAMP-dependent amylin receptor variants are therapeutically relevant across osteoporosis, metabolic disease, obesity, and cardiovascular physiology (Barwell et al. 2012). The peptide serves as a research tool for dissecting which receptor configurations — CTR alone versus AMY1/AMY2/AMY3 — respond to different ligands from the calcitonin/CGRP family, including probing the interaction mechanisms that distinguish calcitonin from amylin signaling (Lee et al. 2016).
Evidence
- Human: No clinical trials for this specific fragment. Its therapeutic context lies in the CTR/amylin receptor system, which is clinically engaged by calcitonin (FDA-approved) and by the amylin analog cagrilintide (in clinical development as part of the CagriSema combination).
- Animal: The calcitonin receptor and its RAMP-dependent amylin receptor isoforms have been studied in multiple animal models of bone metabolism and metabolic disease (Pondel 2000; Granholm et al. 2008).
- In vitro: Peptidomic identification and biological validation of this fragment and its interaction with CTR-family receptors performed in neuroendocrine tissue preparations (Yamaguchi et al. 2007; Lee et al. 2016).
Known effects
- CTR agonism / bone resorption modulation — Preclinical / mechanistic; CTR activation suppresses osteoclast activity (Pondel 2000)
- Amylin receptor engagement — Mechanistic; amylin receptors (CTR + RAMP1/2/3) are the molecular targets relevant to amylin analog pharmacology (Hay et al. 2018)
- Neuroendocrine regulatory activity — Mechanistic; identified as a biologically active neuroendocrine peptide by peptidomic validation (Yamaguchi et al. 2007)
Regulatory status
- US: Not a regulated drug; research peptide only.
- EU: Not approved.
- WADA: Not listed.
Mechanism
CTR is one of two class B (secretin-family) GPCRs in the calcitonin/CGRP receptor system — the other being CLR (calcitonin receptor-like receptor). Receptor pharmacological diversity in this family arises from heterodimerization of CTR or CLR with three receptor activity-modifying proteins (RAMP1, RAMP2, RAMP3), generating the CGRP receptor (CLR/RAMP1), the AM₁ and AM₂ adrenomedullin receptors (CLR/RAMP2 or RAMP3), and the AMY₁, AMY₂, and AMY₃ amylin receptors (CTR/RAMP1, CTR/RAMP2, CTR/RAMP3), as reviewed by Hay and colleagues (2018). The RAMPs act as allosteric modulators of both CTR and CLR, shaping ligand selectivity and signaling output at each receptor complex (Advances in Pharmacology 2020). CGRP I precursor [107–119] is a linear 13-residue fragment with no disulfide bonds, lipidation, or cap modifications; the sequence NNFVPTNVGSKAF is the full active form as identified. Lee and colleagues (2016) examined how calcitonin-family peptides interact with CTR and amylin receptor complexes at the molecular level, providing the mechanistic framework for interpreting this fragment's receptor engagement.
Related peptides
- Calcitonin — the 32-residue peptide hormone that is the primary endogenous CTR agonist in bone physiology; shares the same receptor system as this fragment
- Amylin (IAPP) — pancreatic peptide that signals through CTR/RAMP amylin receptor complexes (AMY1–3); the pharmacological target class most directly relevant to this fragment's research use
- CGRP (calcitonin gene-related peptide) — the 37-residue neuropeptide encoded by the same CGRP I precursor gene, from which this fragment is also derived
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.7362826466560364 | openfold3-mlx |
| ranking score | 0.8372742533683777 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.729 | global PDE — lower = better |
| disorder | 0.214 | fraction disordered |
| chain pair ipTM (A, B) | 0.736 | interface quality |
▸3-letter notation
▸recipeopenfold3-mlx 0.3.1
| parameter | value |
|---|---|
| model | openfold3-mlx 0.3.1 |
| weights | aedd8f3eb814e392… |
| hardware | apple_m4_base_16gb |
| mlx version | 0.31.1 |
| python | 3.14.3 |
| random seed | 42 |
| msa strategy | colabfold |
| diffusion samples | 1 |
| runtime | 414s |
| predicted by | mlx@peptide |
| predicted at | 2026-04-24 |
python3 openfold3/run_openfold.py predict --query_json {query.json} --runner_yaml examples/example_runner_yamls/mlx_runner.yml --output_dir {output_dir} --num_diffusion_samples 1 ▸citationbibtex
@peptide{pep10624,
sequence = {NNFVPTNVGSKAF},
target = {calcr},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}