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| Targets |
Parathyroid hormone receptor type 1 (PTH1R), a class B G-protein-coupled receptor that mediates the actions of both PTH and PTHrP. This peptide acts as a competitive antagonist, binding to the receptor with high affinity (Ki = 69 nM in bovine renal cortical membranes) without inducing the conformational changes necessary for G-protein coupling and downstream signaling activation, thereby blocking the effects of endogenous PTH and PTHrP.
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| ln Vitro |
In opossum kidney (OK) cells, (D-Trp12,Tyr34)-pTH (7-34) amide (0.05–10 μM) inhibits PTHrP or PTH-stimulated cAMP production in a concentration-dependent manner [2]. A 0.1-10 μM amide of (D-Trp12, Tyr34)-pTH (7-34) attenuates the NapiT inhibition induced by 1 nM PTHrP or PTH [2].
(D-Trp12,Tyr34)-pTH(7-34)amide demonstrates potent competitive antagonism of PTH with a Ki of 69 nM in bovine renal cortical membrane preparations. In renal cell models, it effectively inhibits PTH- and PTHrP-stimulated phosphate (Pi) transport and cAMP accumulation, blocking receptor-mediated signal transduction. The peptide shows high affinity binding to the PTH1 receptor and can completely inhibit the biological effects of PTH and PTHrP at nanomolar concentrations in cell-based functional assays. |
| ln Vivo |
In hypercalcemic athymic nude mice harboring human squamous cells, (D-Trp12, Tyr34)-pTH (7-34) amide (1 mg/mL once, 0.1 mg/mL six hours) alters blood calcium levels (iv). No discernible effect on lung cancer [3].
In vivo, this peptide antagonist has been used to study PTH actions in various animal models, but its efficacy is limited by rapid inactivation in plasma, which accounts for its lack of effectiveness in models of hypercalcemia of malignancy. When administered to animal models, it can block PTH-mediated effects on serum calcium and phosphate levels, and urinary cAMP excretion. However, due to its susceptibility to proteolytic degradation, continuous infusion or high-dose administration may be required to achieve sustained receptor blockade. |
| Enzyme Assay |
Competitive radioligand binding assay: Bovine renal cortical membranes (prepared by differential centrifugation) are incubated with 0.1-0.5 nM [¹2⁵I]PTH (or [¹2⁵I]PTHrP) and varying concentrations of the antagonist peptide (0.1-10,000 nM) in binding buffer (50 mM Tris-HCl pH 7.4, 0.1% BSA, 5 mM MgCl2, 0.1 mM PMSF) for 2-4 hours at room temperature. Bound and free radioactivity are separated by rapid filtration through GF/C glass fiber filters pre-soaked in 0.5% polyethyleneimine, followed by washing with ice-cold buffer. Filter-bound radioactivity is quantified by gamma counting. Ki values are calculated from competition curves using nonlinear regression analysis (Cheng-Prusoff equation).
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| Cell Assay |
PTH-stimulated cAMP accumulation assay: Renal epithelial cells (e.g., OK cells or LLC-PK1 cells) expressing endogenous PTH1R are seeded in 24-well plates and pre-incubated with the antagonist peptide (0.1-10,000 nM) for 15-30 minutes in serum-free medium containing 0.1% BSA and 0.5 mM IBMX (phosphodiesterase inhibitor). Cells are then stimulated with 10-100 nM PTH or PTHrP for 10-30 minutes at 37degC. The reaction is terminated by aspiration and addition of 0.1 M HCl. Intracellular cAMP levels are measured by competitive ELISA or RIA. Antagonist potency is determined as the concentration required to inhibit PTH-stimulated cAMP accumulation by 50% (IC50).
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| Animal Protocol |
No extensive in vivo animal studies have been reported specifically for this antagonist. In principle, animal models of calcium metabolism (e.g., thyroparathyroidectomized rats or mice) could be used: animals are administered the peptide via intravenous infusion or subcutaneous injection, and serum calcium, phosphate, and urinary cAMP are measured at multiple time points post-administration. The peptide's ability to block PTH-induced hypercalcemia or bone resorption would be assessed. Due to rapid plasma inactivation, continuous infusion (e.g., via osmotic minipump) or frequent dosing may be necessary.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for this specific peptide are limited. As a 28-amino acid peptide, it is subject to rapid proteolytic degradation in plasma, contributing to a short elimination half-life (typically minutes) and limited in vivo efficacy. Like other peptide therapeutics, oral bioavailability is negligible; administration is typically parenteral (intravenous, subcutaneous, or intraperitoneal). The C-terminal amide modification provides some resistance to carboxypeptidase degradation but does not prevent endopeptidase-mediated cleavage.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for this peptide. As a research compound not intended for therapeutic use, comprehensive toxicological profiling has not been performed. Potential toxicity would relate to its pharmacological effect of blocking PTH/PTHrP signaling, which could disrupt calcium homeostasis and bone metabolism if administered chronically at high doses.
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| References |
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| Additional Infomation |
This is a research peptide, not an approved drug. It serves as a valuable tool for investigating PTH receptor pharmacology and the physiological roles of PTH and PTHrP. It is a synthetic analog of the bovine PTH sequence, modified for enhanced antagonistic activity. It has been used to map the structural determinants of PTH receptor binding and to distinguish PTH-mediated effects from those of other calciotropic hormones.
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| Molecular Formula |
C165H251N49O40S2
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| Molecular Weight |
3625.20
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| CAS # |
118102-98-0
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| Appearance |
White to off-white solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O : ~100 mg/mL (~27.58 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.2758 mL | 1.3792 mL | 2.7585 mL | |
| 5 mM | 0.0552 mL | 0.2758 mL | 0.5517 mL | |
| 10 mM | 0.0276 mL | 0.1379 mL | 0.2758 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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