Bone & calcium signaling peptide (PTHrP 1-37)
A natural protein fragment that activates the same bone-building receptor as parathyroid hormone, helping scientists study how the skeleton grows and how cancer can raise 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.
Named peptide fragment — synthesized for research; ClinicalTrials.gov trials registered for parent compound or class
Fork this card to add platform evidence →
Endogenous peptide fragment — receptor binding/activity established in published literature; CT.gov evidence
Fork this card to add platform evidence →
What this is
PTHrP (1-37) is the first 37 amino acids of parathyroid hormone-related protein, a hormone that the body makes naturally. It is the part of the molecule that binds and switches on the same receptor as parathyroid hormone (PTH) — a receptor called PTH1R that sits on bone and kidney cells and controls how the skeleton is built and how calcium is handled (Gardella 2015). The sequence stored here is the human/mouse/rat form (AVSEHQLLHDKGKSIQDLRRRFFLHHLIAEIHTAEIR), a research peptide used to dissect PTH/PTHrP signaling rather than a marketed drug.
What it does
PTHrP (1-37) binds PTH1R, a class B G-protein-coupled receptor that lives on osteoblasts (bone-building cells) and kidney tubule cells. Activating that receptor drives the cAMP/PKA arm of bone-remodeling signaling and, in pathology, underlies the hypercalcemia seen in cancers that secrete PTHrP (Gardella 2015; Zhao 2019). Because PTHrP (1-37) and the clinical PTH analogs share this same receptor, the 1-37 fragment is widely used in the lab as a comparator for understanding bone-active PTH1R drugs such as teriparatide and abaloparatide (Sato 2021).
Mechanism
PTH1R is a class B GPCR. Cryo-EM structural work on the active human PTH1R-Gs complex shows how the N-terminal residues of PTH-family ligands insert into the seven-transmembrane bundle to trigger Gs coupling and downstream cAMP production (Zhao 2019). PTHrP and PTH share their first ~13 residues in functional identity even though primary sequences diverge, which is why PTHrP (1-37) is competent to fully activate PTH1R the way PTH (1-34) does (Gardella 2015).
Signal duration at PTH1R is itself a regulated variable. Comparative work on three PTH1R ligands — teriparatide (PTH 1-34), abaloparatide (a PTHrP-derived analog), and long-acting PTH — found that all three initiate cAMP signaling with comparable kinetics at the receptor, but differ in how long signaling persists after ligand washout, which contributes to their different effects on bone and mineral metabolism in patients (Sato 2021). PTHrP (1-37) sits in the same pharmacological family and serves as a reference compound for that comparison.
Receptor availability at the cell surface is a second layer of control. A naturally occurring PTH1R isoform missing transmembrane domain 7 (Δe14-PTHR) is expressed in human kidney and buccal epithelial cells; it traffics poorly to the cell surface and dampens signaling by the full-length receptor (Alonso 2011). In bone, the integrin-binding adapter Kindlin-2 modulates PTH1R-driven anabolic signaling in osteoblastic cells, and its loss in mice blunts the bone-mineral-density gain normally produced by intermittent PTH stimulation (Fu 2020). These findings position PTH1R not as an on/off switch but as a node whose output depends on receptor isoform, surface expression, and accessory proteins.
Evidence
- Human: No clinical trials of PTHrP (1-37) as a therapeutic; it is a research tool peptide. Clinical PTH1R agonists in the same pharmacological family (teriparatide, abaloparatide) are approved drugs for osteoporosis; PTHrP (1-37) is used preclinically as their comparator (Sato 2021).
- Animal: PTH1R signaling in bone has been dissected in mouse models, including conditional deletion of Kindlin-2 in osteoblastic cells, where it blunts the bone-volume and bone-mineral-density gain from intermittent PTH stimulation (Fu 2020).
- In vitro: Receptor pharmacology of PTHrP-family ligands at PTH1R is well characterized in heterologous expression systems, including the active-state cryo-EM structure of human PTH1R (Zhao 2019) and side-by-side kinetic comparisons of PTH1R ligands (Sato 2021).
Known effects
- PTH1R activation / cAMP signaling — Mechanistic, in vitro (Gardella 2015; Zhao 2019)
- Osteoblast signaling / bone anabolism (PTH/PTHrP family) — Preclinical (Fu 2020)
- Hypercalcemia driver in PTHrP-secreting tumors (parent protein PTHrP) — Clinical biology (Gardella 2015)
- Reference ligand for teriparatide/abaloparatide comparison — Preclinical (Sato 2021)
Regulatory status
- US: Not a drug. PTHrP (1-37) is a research-grade peptide, not FDA-approved for any indication. PTH1R agonists in the same family that ARE approved drugs include teriparatide (PTH 1-34, approved 2002 for osteoporosis) and abaloparatide (PTHrP-derived analog, approved 2017); PTHrP (1-37) itself is not among them.
- WADA: Not specifically listed by name.
Related peptides
- Teriparatide (PTH 1-34) — the clinically used N-terminal PTH fragment that activates the same PTH1R; the most direct pharmacological cousin.
- Abaloparatide — a PTHrP-derived analog approved for osteoporosis, designed from the same N-terminal PTHrP region as PTHrP (1-37) (Sato 2021).
- Long-acting PTH (LA-PTH) — engineered PTH1R agonist used alongside PTHrP (1-37) in receptor-kinetics studies (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.
Does PTHrP(1-37) cause bone cells to receive a different, more sustained signal from inside the cell compared to the current bone drug PTH(1-34)?
If PTHrP(1-37) drives a stronger internal signal, it could explain why natural PTHrP promotes bone growth in a subtly different way, and could inspire better bone-loss treatments that work longer with fewer daily doses.
Could locking part of PTHrP(1-37) into a rigid ring shape make it survive in the bloodstream long enough to be a once-weekly bone treatment?
If this works, patients with osteoporosis might switch from daily injections to weekly or monthly ones, a significant quality-of-life improvement for the large number of people who find daily self-injection burdensome.
Do the three extra amino acids at the end of PTHrP(1-37), compared to existing bone drugs, cause the receptor to stay switched on for a different amount of time?
If true, it could explain why natural PTHrP has different effects on bone than synthetic drugs, and might guide the design of next-generation bone-building medicines with fewer calcium-related side effects.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.8368420004844666 | openfold3-mlx |
| ranking score | 0.9542047381401062 | openfold3-mlx |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.821 | global PDE — lower = better |
| disorder | 0.310 | ! high disorder |
| chain pair ipTM (A, B) | 0.837 | 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 | 868s |
| 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{pep10504,
sequence = {AVSEHQLLHDKGKSIQDLRRRFFLHHLIAEIHTAEIR},
target = {pth1r},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}