GS-5759
Based on 1 Customer Validation
GS-5759 is a PDE4 inhibitor and β2-adrenoceptor agonist. GS-5759 synergistically elevates intracellular cAMP levels and upregulates the expression of related anti-inflammatory genes by agonizing β2-adrenoceptor (β2AR) (KA = 0.76 nM) and inhibiting PDE4 (IC50 = 1.38 nM), thereby exerting a potent dual bronchodilatory and anti-inflammatory effect. GS-5759 can be used for research on respiratory diseases such as chronic obstructive pulmonary disease (COPD).
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
- Reinheit : 99.52%
- CAS. Nr.: 1346653-91-5
- Formel: C47H42N6O8S
- Molecular Weight:850.94
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Speicherung:
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biologische Aktivität
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Chemical Information
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Lösungsmittel & Löslichkeit
- Protokoll
- Reinheit & Dokumentation
- Verweise
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Help & FAQs
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Biologische Aktivität
Beschreibung
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PDE4 1.38 nM (IC50) |
β2 adrenoceptor 0.76 nM (KA) |
TNF-α |
In Vitro
GS-5759 (6 h) activates CRE-dependent luciferase in BEAS-2B cells in a concentration-dependent manner with a Hill coefficient of 1.91, and in this reporter gene assay its potency is 29-fold higher than that at PDE4B1[4].
GS-5759 binds to β2-adrenergic receptors in BEAS-2B with KA = 0.76 nM and exhibits high operational efficacy[4].
GS-5759 (up to approximately 100 nM; 6 h) potently activates CRE-dependent transcriptional/luciferase activity in 6×CRE BEAS-2B reporter cells (p[A]50 = 10.41), with higher potency than the monofunctional β2 receptor agonist parent compound.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
GS-5759 (10-103 µg/kg; i.t.; single dose) does not significantly increase heart rate or mean blood pressure at the high doses tested in the beagle dog model, with a safety index >31[1].
GS-5759 (3.3 mg/kg; i.t.; twice daily) inhibits cigarette smoke-induced pulmonary neutrophilia in a cigarette smoke-induced lung inflammation model in C3H/HeN mice[1].
GS-5759 (2-700 µg/kg; i.t. single dosing) dose-dependently inhibits LPS-induced pulmonary neutrophilia in cynomolgus monkeys, with an ED50 of 4.9 µg/kg[1].
GS-5759 (7-133 µg/kg; i.t.; single dose) has a protective effect against bronchoconstriction in the MCh (HY-P1205)-induced pulmonary resistance model in cynomolgus monkeys, reaching maximum inhibition at 70 µg/kg[1].
GS-5759 (1.4-18.2 µg/kg; i.t.; single administration) dose-dependently protects sensitized beagle dogs from antigen-induced bronchoconstriction in the Pollen extract, ragweed (HY-NP179B)-induced beagle dog pulmonary resistance model, with an ED50 of 3.4 µg/kg[1].
GS-5759 (300-3000 µg/kg; i.t.; single dose; 3 h) has no emetogenic side effects in the ferret emesis model[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Dunkin-Hartley (male, 500-700 g) (ACh-induced bronchoconstriction model).[1]
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Dosage:6.2, 62, and 124 µg/kg
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Administration:i.t.; single dose; baseline measurement 24h before ACh challenge, challenges and measurements at 4, 8, and 24h post-dosing
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Result:Dose- and time-dependently inhibited ACh-induced bronchoconstriction, with the highest dose exhibiting 77% inhibition at 4 hours.
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Animal Model:Cynomolgus monkeys[1]
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Dosage:22, 70, 133 µg/kg (lung resistance); 2, 7, 70, 700 µg/kg (inflammation)
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Administration:i.t.; single dose; MCh challenge 2h post-dosing, or LPS exposure for 15 min at 2h post-dosing with BAL analysis at 24h
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Result:Dose-dependently inhibited the MCh-induced increase in lung resistance, reaching a plateau of maximum inhibition at 70 µg/kg.
Dose-dependently inhibited LPS-induced neutrophilia with an ED50 of 4.9 µg/kg.
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Animal Model:Beagle (male, 2.5-4 years, ragweed-sensitized)[1]
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Dosage:1.4, 5.5, 18.2 µg/kg (resistance); 10, 50, 103 µg/kg (cardiovascular)
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Administration:i.t.; single dose; antigen challenge for 30 min at 1h post-dosing to measure resistance, or continuous monitoring of heart rate/blood pressure for 200 min post-dosing
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Result:Dose-dependently inhibited antigen-induced increase in pulmonary resistance with an ED50 of 3.4 µg/kg.
Did not significantly increase heart rate or mean blood pressure at the tested doses (up to 103 µg/kg), yielding a therapeutic index > 31.
Chemical Information
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CAS. Nr. 1346653-91-5
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Appearance Solid
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Molecular Weight 850.94
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Formel C47H42N6O8S
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Color Light yellow to yellow
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SMILES
O=C(C1=C(NC2=CC=CC(OC)=C2)C3=CC(S(=O)(C4=CC=CC(C(NC5=CC=C(C#CCCCNC[C@@H](C6=CC=C(O)C7=C6C=CC(N7)=O)O)C=C5)=O)=C4)=O)=CC(C)=C3N=C1)N
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
Lösungsmittel & Löslichkeit
In Vitro:
DMSO : 100 mg/mL (117.52 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (2.94 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Reinheit & Dokumentation
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Data Sheet (281 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
Verweise
[1]. Salmon M, et al. The in vivo efficacy and side effect pharmacology of GS-5759, a novel bifunctional phosphodiesterase 4 inhibitor and long-acting β 2-adrenoceptor agonist in preclinical animal species. Pharmacology research & perspectives. 2014 Aug;2(4):e00046. [Content Brief]
[2]. Forkuo GS, et al. Phosphodiesterase 4 inhibitors attenuate the asthma phenotype produced by β2-adrenoceptor agonists in phenylethanolamine N-methyltransferase–knockout mice. American journal of respiratory cell and molecular biology. 2016 Aug;55(2):234-42. [Content Brief]
[4]. Joshi T, et al. GS-5759, a Bifunctional β2-Adrenoceptor Agonist and Phosphodiesterase 4 Inhibitor for Chronic Obstructive Pulmonary Disease with a Unique Mode of Action: Effects on Gene Expression in Human Airway Epithelial Cells. The Journal of pharmacology and experimental therapeutics. 2017 Feb;360(2):324-340. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.1752 mL | 5.8759 mL | 11.7517 mL | 29.3793 mL |
| 5 mM | 0.2350 mL | 1.1752 mL | 2.3503 mL | 5.8759 mL | |
| 10 mM | 0.1175 mL | 0.5876 mL | 1.1752 mL | 2.9379 mL | |
| 15 mM | 0.0783 mL | 0.3917 mL | 0.7834 mL | 1.9586 mL | |
| 20 mM | 0.0588 mL | 0.2938 mL | 0.5876 mL | 1.4690 mL | |
| 25 mM | 0.0470 mL | 0.2350 mL | 0.4701 mL | 1.1752 mL | |
| 30 mM | 0.0392 mL | 0.1959 mL | 0.3917 mL | 0.9793 mL | |
| 40 mM | 0.0294 mL | 0.1469 mL | 0.2938 mL | 0.7345 mL | |
| 50 mM | 0.0235 mL | 0.1175 mL | 0.2350 mL | 0.5876 mL | |
| 60 mM | 0.0196 mL | 0.0979 mL | 0.1959 mL | 0.4897 mL | |
| 80 mM | 0.0147 mL | 0.0734 mL | 0.1469 mL | 0.3672 mL | |
| 100 mM | 0.0118 mL | 0.0588 mL | 0.1175 mL | 0.2938 mL |
GS-5759 Related Classifications
HY-120246 Related Classifications
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Keywords
- GS-5759
- 1346653-91-5
- GS5759
- GS 5759
- Adrenergic Receptor
- Phosphodiesterase (PDE)
- TNF Receptor
- CCR
- Beta Receptor
- Tumor Necrosis Factor Receptor
- TNFR
- CC chemokine receptor
- COPD
- PDE4 inhibitor
- PDE4B1
- TNF-α
- anti-inflammatory
- bronchodilation
- cAMP
- obstructive airway diseases
- pulmonary neutrophilia
- β2-adrenoceptor agonist
- Inhibitor
- inhibitor
- inhibit