PCO371 |
رقم الكتالوجGC32415
One-Click Copy Product Info
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PCO371 هو مفعول كامل عن طريق الفم لمستقبل هرمون جريان الدم إلى الغدة الدرقية 1 (PTHR1)، دون تأثير على مستقبل نوع PTH 2.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1613373-33-3
Sample solution is provided at 25 µL, 10mM.
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PCO371 is an orally active small-molecule full agonist of the PTHR1, which binds to the intracellular interface of PTH1R and the Gs protein[1-2]. PCO371 can be used in research on PTH-related diseases such as hypoparathyroidism[3].
In vitro, PCO371 (0.1nM–0.1mM) stimulated COS-7 cells expressing human PTH1R and UMR-106 rat osteosarcoma cells expressing endogenous rat PTH1R for 20 minutes or 6 hours. PCO371 dose-dependently stimulated intracellular cAMP production and activated the phospholipase C signaling pathway. PCO371 dose-dependently increased the mRNA expression of Fos, osteocalcin, and RANKL, and decreased the mRNA expression of osteoprotegerin and sclerostin[4]. PCO371 (10nM–100μM) treated LLC-PK1 cells stably expressing the human parathyroid hormone 1 receptor (hPTHR1) for 5-120 minutes. PCO371 activated the receptor in a concentration-dependent manner and increased intracellular cAMP production[5].
In vivo, PCO371 (30mg/kg orally; once daily) was administered for 12 weeks to 32-week-old ovariectomized rats. PCO371 significantly increased bone turnover markers. PCO371 had limited effects on improving bone mineral density and bone strength[4]. A single oral administration of PCO371 (30mg/kg) was given to thyroparathyroidectomized (TPTX) rats. PCO371 significantly increased serum calcium concentration and decreased serum phosphate concentration in mice[5].
References:
[1] Zhao LH, He Q, Yuan Q, et al. Conserved class B GPCR activation by a biased intracellular agonist. Nature. 2023 Sep;621(7979):635-641.
[2] Kobayashi K, Kawakami K, Kusakizako T, et al. Class B1 GPCR activation by an intracellular agonist. Nature. 2023 Jun;618(7967):1085-1093.
[3] Nishimura Y, Esaki T, Isshiki Y, et al. Synthesis and Biological Evaluations of Novel Human Parathyroid Hormone 1 Receptor (hPTHR1) Agonists Bearing Bicyclic Aromatic Moiety. ChemMedChem. 2024 Mar 1;19(5):e202300589.
[4] Tamura T, Noda H, Joyashiki E, et al. Identification of an orally active small-molecule PTHR1 agonist for the treatment of hypoparathyroidism. Nat Commun. 2016 Nov 18;7:13384.
[5] Nishimura Y, Esaki T, Isshiki Y, et al. Lead Optimization and Avoidance of Reactive Metabolite Leading to PCO371, a Potent, Selective, and Orally Available Human Parathyroid Hormone Receptor 1 (hPTHR1) Agonist. J Med Chem. 2020 May 28;63(10):5089-5099.
| Cell experiment [1]: | |
Cell lines | COS-7 cells (monkey kidney fibroblast-like cell line), UMR-106 cells (rat osteosarcoma cell line) |
Preparation Method | COS-7 cells were transfected to express human PTHR1 (hPTHR1). Cells were treated with PCO371 (0.1nM–0.1mM) in assay medium containing BSA and the phosphodiesterase inhibitor IBMX. UMR-106 cells expressing endogenous rat PTHR1 were also treated with PCO371 in similar assay medium for cAMP measurement or in DMEM with 0.2% BSA for gene expression analysis. |
Reaction Conditions | 0.1nM–0.1mM; 20 minutes or 6h |
Applications | PCO371 dose-dependently stimulated cAMP production in hPTHR1-expressing COS-7 cells (EC₅₀=2.4μM) and also activated the phospholipase C signaling pathway (EC₅₀=17μM). In UMR-106 cells, PCO371 induced cAMP production and altered the expression of bone-related mRNAs. |
| Animal experiment [2]: | |
Animal models | Thyroparathyroidectomized (TPTX) rats |
Preparation Method | TPTX rats with serum calcium levels <8.0mg/dL received a single oral administration of PCO371 (30mg/kg). Blood was collected from the jugular vein immediately before and at 0.5, 1, 2, 4, 6, 10, and 24 hours after administration to measure serum calcium and phosphate levels. |
Dosage form | 30mg/kg; p.o.; Single administration. |
Applications | A single oral administration of PCO371 dose-dependently increased serum calcium concentration and decreased serum phosphate concentration. The calcemic action of PCO371 was more prolonged than that of its lead compound or a single subcutaneous administration of hPTH(1-34). |
References: | |
| Cas No. | 1613373-33-3 | SDF | |
| Canonical SMILES | FC(F)(F)OC1=CC=C(C2=NC3(CCN(S(CCC4=C(C)C=C(N5C(NC(C5(C)C)=O)=O)C=C4C)(=O)=O)CC3)C(N2)=O)C=C1 | ||
| Formula | C29H32F3N5O6S | M.Wt | 635.65 |
| الذوبان | DMSO: 125 mg/mL (196.65 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.5732 mL | 7.866 mL | 15.7319 mL |
| 5 mM | 314.6 μL | 1.5732 mL | 3.1464 mL |
| 10 mM | 157.3 μL | 786.6 μL | 1.5732 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >95.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 22 reference(s) in Google Scholar.)