Bone-and-calcium-signaling peptide (PTHrP 1-40)
A natural human protein fragment that activates the same receptor as parathyroid hormone, influencing bone formation and blood calcium levels; used only as a lab research tool.
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
PTH-related protein (1-40), or PTHrP(1-40), is the first 40 amino acids of a natural human protein called parathyroid hormone-related protein (PTHrP). The N-terminal end of PTHrP looks a lot like the N-terminal end of parathyroid hormone (PTH) itself — they share 8 of their first 16 amino acids — and that resemblance is why both proteins can bind and activate the same receptor on bone and kidney cells (Moseley 1987). PTHrP was originally purified from a human lung cancer cell line where its PTH-like activity was causing the high blood calcium seen in some cancer patients (Moseley 1987). This 1-40 synthetic fragment is a research tool used to study how PTHrP's active end engages that shared receptor.
History
PTHrP was identified in the 1980s as the factor responsible for humoral hypercalcemia of malignancy — a syndrome in which certain tumors raise a patient's blood calcium by secreting something with PTH-like activity. Moseley and colleagues (PNAS, 1987) purified the protein from serum-free medium of the BEN human lung cancer cell line, isolated an 18 kDa active species, and obtained N-terminal sequence showing partial identity with human PTH. That homology placed both proteins on the same receptor — later named PTH1R — and made the N-terminal fragments of PTH and PTHrP the workhorse ligands for studying that receptor.
What it does
PTHrP(1-40) acts on the type 1 parathyroid hormone receptor (PTH1R), the same receptor used by PTH and by clinical PTH analogs. PTH1R is a class B G-protein-coupled receptor and a central regulator of skeletal development and homeostasis (Fu 2020, Gardella 2015). In bone, intermittent stimulation of this receptor by PTH-family ligands increases bone volume fraction and bone mineral density — a bone-building effect that has been demonstrated in mice and that depends on intact PTH1R signaling in osteoblastic cells (Fu 2020). In the kidney, the same receptor regulates calcium and phosphate handling (Lee 2009).
Mechanism
PTH1R belongs to family B of the G-protein-coupled receptors and signals through multiple pathways, including Gαs/cAMP and Gαq/PLC arms (Gardella 2015). Different N-terminal ligands engage the receptor with distinct kinetics and signaling profiles: a comparative study of teriparatide (hPTH 1-34), abaloparatide, and a long-acting PTH analog found that although all three bind PTH1R and trigger overlapping intracellular pathways, they differ in the duration and balance of those signals — differences that translate into different skeletal and mineral-metabolism effects in patients (Sato 2021). PTH1R signaling can also be tuned at the receptor level: a naturally occurring human isoform that lacks transmembrane domain 7 (Δe14-PTHR) shows reduced cell-surface expression and dampened signaling, and acts as a negative modulator of the full-length receptor (Alonso 2011).
PTHrP(1-40) extends the canonical 1-34 active fragment by six C-terminal residues. The stored sequence here is AVSEHQLLHDKGKSIQDLRRRFFLHHLIAEIHTAEIRATS — the unmodified human/mouse/rat (1-40) backbone, with no fatty-acid conjugation or other half-life-extending chemistry.
Evidence
- Human: No clinical trials of PTHrP(1-40) itself. Clinically, the related PTHrP(1-34) analog abaloparatide and the PTH(1-34) analog teriparatide are used in patients with osteoporosis and hypoparathyroidism through the same PTH1R (Sato 2021).
- Animal: Intermittent PTH stimulation of PTH1R in osteoblastic cells increases bone volume fraction and bone mineral density in mice; this effect is impaired when Kindlin-2 is deleted in those cells (Fu 2020).
- In vitro: Comparative cell-based work shows teriparatide, abaloparatide, and long-acting PTH all engage PTH1R but differ in the duration and balance of downstream signals (Sato 2021); a Δe14-PTHR isoform with truncated transmembrane domain 7 shows reduced surface expression and dampened signaling relative to full-length PTHR (Alonso 2011).
Related peptides
- Teriparatide (recombinant PTH 1-34) — the clinically used PTH N-terminal fragment that, like PTHrP(1-40), engages PTH1R for bone anabolic effect (Sato 2021).
- Abaloparatide — a PTHrP(1-34) analog used clinically for osteoporosis, sharing the PTHrP N-terminus with the peptide on this card (Sato 2021).
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.
Can the same signal that shapes bone tissue stop dangerous calcium deposits from forming inside blood vessels?
Calcium deposits in arteries are a leading cause of heart attacks and strokes, especially in people with kidney disease or diabetes. If this peptide can reverse the process that drives that buildup, it could open a new treatment path for patients who currently have very few options.
Can changing two amino acids in this peptide stop the body from breaking it down too fast?
Peptide drugs for bone loss tend to break apart in the blood within minutes, which is why patients need daily injections. If this specific chemical swap holds up, it could be the first step toward a longer-lasting form of the drug, potentially reducing how often people need to inject it.
Do the six extra building blocks at the end of this peptide cause it to grip its receptor longer and keep the signal going?
Current bone-building drugs work but produce a signal that fades quickly. If this slightly longer peptide holds on to its receptor longer, it might sustain the bone-building signal more effectively, which could translate into better outcomes for people with osteoporosis.
Does this peptide keep a key bone-cell switch flipped off for longer than the standard osteoporosis drug?
Teriparatide is the leading bone-building drug, but its effect on bone cells is brief. If PTHrP(1-40) suppresses the same cellular brake for a longer window, it might build bone more efficiently, giving researchers a clearer target for next-generation osteoporosis treatments.
Does this peptide stick to the bone receptor much more than to a related receptor found in the brain and other organs?
When a research compound activates receptors in unintended tissues, it muddies the results and raises safety concerns. If this peptide proves highly selective for the bone receptor, scientists could use it to study bone biology much more cleanly, and drug developers could design therapies with a lower risk of side effects elsewhere in the body.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.8358373641967773 | openfold3-mlx |
| ranking score | 0.9490659832954407 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.767 | global PDE — lower = better |
| disorder | 0.294 | fraction disordered |
| chain pair ipTM (A, B) | 0.836 | 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 | 1081s |
| 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{pep10505,
sequence = {AVSEHQLLHDKGKSIQDLRRRFFLHHLIAEIHTAEIRATS},
target = {pth1r},
author = {peptidemodel},
year = {2026},
status = {synthesized}
}