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| Other Sizes |
Purity: ≥98%
| Targets |
PCO371 targets the parathyroid hormone type 1 receptor (PTHR1), a G protein-coupled receptor that plays a critical role in calcium homeostasis and bone metabolism. It is a selective agonist that does not affect PTHR2. Activation of PTHR1 by PCO371 stimulates cAMP production, mimicking the action of endogenous parathyroid hormone.
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| ln Vitro |
Orally administered PCO371 is a complete agonist that is active on parathyroid hormone receptor 1 (PTHR1) and does not bind to PTH 2 receptors. With an EC50 of 2.4 μM in COS-7 cells expressing hPTHR1 and 2.5 μM in COS-7 cells transfected with hPTHR1-delNT, PCO371 promotes the generation of cAMP and increases phospholipase C activity (EC50, 17 μM) [1].
PCO371 stimulates cAMP production in COS-7 cells with an EC50 of 2.4 μmol/L. This in vitro activity confirms its function as a PTHR1 agonist and demonstrates its potency in a cellular context. The compound's ability to activate PTHR1-mediated signaling pathways has been characterized in these cell-based assays, establishing its efficacy as a non-peptidyl agonist. |
| ln Vivo |
In vivo, PCO371 significantly enhances bone mineral density (BMD) and bone strength in the lumbar vertebrae of osteopenic ovariectomized (OVX) rats, an animal model of postmenopausal osteoporosis. It also restores normal serum calcium levels without increasing urinary calcium in hypocalcemic thyroparathyroidectomized (TPTX) rats. These effects support its potential as an orally active therapeutic for osteoporosis.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays typically involve competitive binding experiments using radiolabeled ligands or functional assays measuring second messenger production, such as cAMP, in membrane preparations or whole cells expressing the PTHR1 receptor. The EC50 value of 2.4 μmol/L was determined using such methods.
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| Cell Assay |
In vitro cellular assays for PCO371 involve treating PTHR1-expressing cells, such as COS-7 cells, with varying concentrations of the compound. The production of cAMP is then measured using standard biochemical detection methods to quantify receptor activation. The EC50 is determined from the dose-response curve.
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| Animal Protocol |
In vivo animal experiments for PCO371 have been conducted in osteopenic ovariectomized (OVX) rats, a model for osteoporosis. The compound was administered orally, and its effects on bone mineral density and bone strength were assessed. Additionally, its effects on serum calcium were evaluated in hypocalcemic thyroparathyroidectomized (TPTX) rats.
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| ADME/Pharmacokinetics |
PCO371 is orally active, suggesting favorable oral bioavailability. It is soluble in DMSO (100 mg/mL) and ethanol (2 mg/mL) but insoluble in water. For in vivo administration, a homogeneous suspension in CMC-Na (≥5 mg/mL) or a clear solution using 5% DMSO, 40% PEG300, 5% Tween 80, and 50% ddH2O are validated formulations.
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| Toxicity/Toxicokinetics |
Available information does not specify detailed toxicity data for PCO371. As a research compound, its safety profile is still under investigation. Standard toxicological studies would be required to determine its safety for clinical use. Its development as an osteoporosis drug suggests a focus on bone-related safety endpoints.
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| References | |
| Additional Infomation |
PCO-371 is being investigated in the clinical trial NCT02475616 (a single-dose escalation study of PCO371 in healthy volunteers).
PCO371 is a research compound being developed as a potential treatment for osteoporosis. Its mechanism of action involves the activation of the PTHR1 receptor, which plays a key role in bone metabolism. As a non-peptidyl agonist, it offers the advantage of oral administration compared to peptide-based PTH therapies. It has not yet received regulatory approval for clinical use. |
| Molecular Formula |
C29H32F3N5O6S
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|---|---|
| Molecular Weight |
635.654496192932
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| Exact Mass |
635.202
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| CAS # |
1613373-33-3
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| PubChem CID |
76283707
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.636
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| LogP |
4.56
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
44
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| Complexity |
1270
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
LDZJFVOUPUFOHX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H32F3N5O6S/c1-17-15-20(37-26(40)34-24(38)27(37,3)4)16-18(2)22(17)9-14-44(41,42)36-12-10-28(11-13-36)25(39)33-23(35-28)19-5-7-21(8-6-19)43-29(30,31)32/h5-8,15-16H,9-14H2,1-4H3,(H,33,35,39)(H,34,38,40)
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| Chemical Name |
1-(3,5-dimethyl-4-(2-((4-oxo-2-(4-(trifluoromethoxy)phenyl)-1,3,8-triazaspiro[4.5]dec-1-en-8-yl)sulfonyl)ethyl)phenyl)-5,5-dimethylimidazolidine-2,4-dione
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| Synonyms |
PCO371 PCO-371 PCO 371.
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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 |
| 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) |
DMSO : ~100 mg/mL (~157.32 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (9.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 6.25 mg/mL (9.83 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 62.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 6.25 mg/mL (9.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5732 mL | 7.8660 mL | 15.7319 mL | |
| 5 mM | 0.3146 mL | 1.5732 mL | 3.1464 mL | |
| 10 mM | 0.1573 mL | 0.7866 mL | 1.5732 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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