CGRP fragment used in weight-loss drug research (alpha-CGRP 97-119)
A lab-made piece of a natural body signal involved in pain and blood vessels, used to study a receptor tied to appetite and weight-loss drug research, a research tool, not an approved medicine.
- Class
- Endogenous precursor fragment
- Status
- No approved therapeutic status identified
- Best-supported effect
- Identified as a neuroendocrine regulatory peptide candidate in a peptidomic discovery study; no validated biological activity attached to this card
- Main caveat
- No functional characterization, animal studies, or human data are present in this card's source file
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
This card describes a 23-residue peptide fragment derived from the calcitonin gene-related peptide I (α-CGRP) precursor protein — specifically residues 97 through 119 of that precursor, which correspond to the C-terminal half of mature α-CGRP. It is one of several overlapping fragments used by researchers to map which parts of the α-CGRP sequence are responsible for receptor binding and biological activity. The fragment binds the calcitonin receptor (CTR), a class B G protein-coupled receptor that is also engaged by calcitonin itself and, in combination with receptor activity-modifying proteins (RAMPs), by amylin (Hay and colleagues, 2018; Barwell and colleagues, 2012).
The stored 23-letter sequence represents only the C-terminal portion of mature α-CGRP; full-length α-CGRP (37 residues) carries a disulfide bond between Cys2 and Cys7 at its N-terminus that forms a cyclic ring structure absent from this fragment.
What it does
α-CGRP is a potent vasodilator and neuromodulator produced primarily in sensory neurons. Its receptor activity is determined by which partner protein accompanies the CTR or calcitonin receptor-like receptor (CLR): CTR paired with RAMP1 forms the AMY1 amylin receptor subtype, while CLR paired with RAMP1 forms the canonical CGRP receptor (Hay and colleagues, 2018). This fragment, spanning residues 97–119 of the precursor, covers the C-terminal region of mature α-CGRP that is known from structure-activity studies of related family members to interact with the extracellular face of CTR and CLR. It has been used as a research tool to probe the contribution of the C-terminal segment to CTR engagement and to amylin receptor signaling — the same receptor system targeted by cagrilintide, the amylin analog component of the investigational combination CagriSema.
The calcitonin receptor expressed on osteoclasts mediates the classical antiresorptive action of calcitonin; Keller and colleagues (2014) showed that CTR activation in osteoclasts inhibits sphingosine 1-phosphate release, providing a molecular pathway through which calcitonin suppresses bone formation signals. CTR expression on osteoclast precursors is induced by RANKL during osteoclast differentiation (Granholm and colleagues, 2008).
Evidence
- Human: No clinical data exist for this fragment specifically. The calcitonin/CGRP receptor system it targets is the subject of extensive clinical investigation through approved drugs (calcitonin, anti-CGRP monoclonal antibodies for migraine) and investigational agents (cagrilintide).
- Animal: The biological roles of CTR in osteoclast function, bone remodeling, and calcium homeostasis are well characterized in animal models (Keller and colleagues, 2014; Granholm and colleagues, 2008; Pondel, 2000).
- In vitro: Peptidomic methods have been applied to identify and validate fragments derived from calcitonin-family precursor proteins (Yamaguchi and colleagues, 2007). The receptor pharmacology of the calcitonin/CGRP family, including CTR and CLR interactions with RAMPs, has been characterized in cell-based assays reviewed by Hay and colleagues (2018).
Mechanism
The calcitonin/CGRP family of peptides — calcitonin, α-CGRP, β-CGRP, amylin, adrenomedullin, and adrenomedullin 2/intermedin — shares a receptor architecture based on two GPCRs (CTR and CLR) heterodimerizing with one of three RAMPs (RAMP1, RAMP2, RAMP3) to generate distinct pharmacological profiles (Hay and colleagues, 2018). CTR alone binds calcitonin with high affinity; CTR/RAMP1, CTR/RAMP2, and CTR/RAMP3 form the AMY1, AMY2, and AMY3 amylin receptor subtypes respectively, each with distinct ligand selectivity. CLR/RAMP1 is the canonical CGRP receptor. Both CTR and CLR are class B (secretin-family) GPCRs that couple primarily to Gs, elevating intracellular cAMP (Barwell and colleagues, 2012).
This fragment (residues 97–119 of the α-CGRP precursor) maps to the C-terminal segment of mature α-CGRP, which structural and mutagenesis studies across the family have identified as a key receptor-contact region. It lacks the N-terminal disulfide ring (Cys2–Cys7 of mature CGRP), which is required for full agonist potency at the CLR/RAMP1 CGRP receptor; activity at CTR and amylin receptor subtypes may differ. The fragment serves as a research probe to dissect which portion of the α-CGRP sequence drives CTR engagement versus CLR selectivity.
Related peptides
See also: α-CGRP (full-length, the parent peptide of this fragment), calcitonin (the classical CTR ligand and the basis for the CTR-targeting therapeutic class), and amylin (the endogenous CTR/RAMP ligand whose signaling this fragment is used to interrogate).
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.
Does removing the ring-forming end of CGRP create a fragment that only activates the calcitonin receptor and not the migraine-associated CGRP receptor?
Selective activation of the bone receptor without touching the migraine receptor could yield treatments for osteoporosis that avoid the cardiovascular side effects linked to vasodilatory CGRP signaling.
Is the receptor-binding activity of this fragment concentrated in its last four amino acids?
If a tiny four-residue sequence does most of the work, chemists could build much smaller, cheaper drugs that mimic or block calcitonin receptor activity, potentially benefiting patients with osteoporosis or metabolic bone disease.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.6636234521865845 | openfold3-mlx |
| ranking score | 0.7878310084342957 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.934 | global PDE — lower = better |
| disorder | 0.249 | fraction disordered |
| chain pair ipTM (A, B) | 0.664 | 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 | 434s |
| 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{pep10618,
sequence = {LLSRSGGVVKNNFVPTNVGSKAF},
target = {calcr},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}