GDC-3280
Based on 1 Customer Validation
GDC-3280 (AK3287) is an orally active anti-fibrotic agent. GDC-3280 inhibits ASK1 phosphorylation, blocks downstream p38 MAPK activation, reduces NF-κB p65 phosphorylation, elevates IκBα, and reverses PPAR-γ upregulation. GDC-3280 inhibits apoptosis. GDC-3280 ameliorates silica-induced pulmonary dysfunction, inflammation, and fibrosis in silicosis models. GDC-3280 can be used for research on silicosis and idiopathic pulmonary fibrosis.
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- Pureté : 98.82%
- CAS No.: 1590403-33-0
- Formule: C18H14F3N5O2
- Masse moléculaire:389.33
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Stockage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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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Activité biologique
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Chemical Information
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Solvant et solubilité
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
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Activité biologique
Description
IC50 & Target
[1]|
IKKα |
PPAR-γ |
TNF-α |
IL-6 |
IL-1β |
In Vitro
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:RAW 264.7 mouse macrophages
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Concentration:100, 200 μg/mL
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Incubation Time:6 h (pre-treatment); 24 h (post-treatment)
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Result:Inhibited silica-induced secretion of IL-1β, IL-6, TNF-α, and TGF-β.
Showed superior effects at 200 μg/mL compared to 100 μg/mL.
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Cell Line:RAW 264.7 mouse macrophages
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Concentration:200 μg/mL
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Incubation Time:6 h (pre-treatment); 24 h (post-treatment)
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Result:Decreased silica-induced cell apoptosis in both pre-treated and post-treated models.
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Cell Line:RAW 264.7 mouse macrophages
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Concentration:200 μg/mL
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Incubation Time:6 h
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Result:Blocked the activation of the ASK1-p38 MAPK signaling pathway in macrophages exposed to silica.
In Vivo
GDC-3280 (100 mg/kg; p.o.; twice a day; 28 days) ameliorates silicosis by blocking the ASK1-p38 MAPK signaling pathway, inhibiting apoptosis, and regulating macrophage polarization in mice[1].
GDC-3280 (100 mg/kg; p.o.; twice a day; 28 days starting at day 14 after silica exposure) improves lung function, alleviates pulmonary inflammation, and delays fibrosis in a silicosis mouse model[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (male, 10-11 weeks old, 24-26 g, intratracheal crystalline silica-induced silicosis)[1]
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Dosage:100 mpk
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Administration:p.o.; twice a day; 28 days
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Result:Alleviated impairment of lung function by increasing inspiratory capacity (IC) and decreasing respiratory resistance (Rrs), elastic resistance (Ers), and tissue damping (G).
Alleviated imaging damages in micro-chest CT.
Reduced pathological changes including nodules, alveolar collapse, thickened alveolar septa, inflammatory cell infiltration, and interstitial edema.
Reduced protein expression of TNF-α, IL-6, and IL-1β in BALF and mRNA expressions in lung tissues.
Demonstrated less extracellular matrix (ECM) deposition.
Downregulated hydroxyproline (HYP) in tissue homogenate.
Decreased deposition levels of collagen I, fibronectin, and α-SMA.
Reduced protein expression of TGF-β, IL-4, and IL-10 in BALF.\nInhibited silica-induced phosphorylation of ASK1 and p38.
Decreased the number of TUNEL-positive cells.
Reduced the accumulation of M1 and M2 macrophages.
Decreased mRNA and protein levels of iNOS and Arg1.
Reduced the ratio of phosphorylated NF-κB to total NF-κB and elevated the expression of IκBα.
Reversed the upregulation of PPAR-γ.
- Kinase activity and phosphorylation assays
- Fibrosis/Collagen Morphometry
- Western Blot
- Collagen: Sirius Red Staining
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Annexin V plus membrane-impermeant dye apoptosis staining
- Connective Tissue: Masson's Trichrome/Collagen Trichrome Staining
- Apoptosis Solutions
- Protocol for Kinase activity and phosphorylation assays
- Research Protocol for Inflammation-related Diseases
Chemical Information
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CAS No. 1590403-33-0
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Appearance Solid
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Masse moléculaire 389.33
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Formule C18H14F3N5O2
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Color White to off-white
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SMILES
O=C1C2=C(C(C3=CN(C)N=C3)=CN1C4=CC=C(C=C4)OC(F)(F)F)N(C)C=N2
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Synonyms
AK3287; AKEX0011
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvant et solubilité
In Vitro:
DMSO : 31.25 mg/mL (80.27 mM; ultrasonic and warming and heat to 60°C; 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. 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. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Pureté et documentation
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Fiche technique (284 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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Instruction de manipulation (2659 KB)
Références
[1]. Fan M, et al. Corrigendum: A novel N-arylpyridone compound alleviates the inflammatory and fibrotic reaction of silicosis by inhibiting the ASK1-p38 pathway and regulating macrophage polarization. Frontiers in pharmacology. 2022;13:1109002. [Content Brief]
[2]. Cheung D, et al. A phase 1, randomized study to evaluate safety, tolerability, and pharmacokinetics of GDC-3280, a potential novel anti-fibrotic small molecule, in healthy subjects. Pulmonary pharmacology & therapeutics. 2021 Aug;69:102051. [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. 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 | 2.5685 mL | 12.8426 mL | 25.6852 mL | 64.2129 mL |
| 5 mM | 0.5137 mL | 2.5685 mL | 5.1370 mL | 12.8426 mL | |
| 10 mM | 0.2569 mL | 1.2843 mL | 2.5685 mL | 6.4213 mL | |
| 15 mM | 0.1712 mL | 0.8562 mL | 1.7123 mL | 4.2809 mL | |
| 20 mM | 0.1284 mL | 0.6421 mL | 1.2843 mL | 3.2106 mL | |
| 25 mM | 0.1027 mL | 0.5137 mL | 1.0274 mL | 2.5685 mL | |
| 30 mM | 0.0856 mL | 0.4281 mL | 0.8562 mL | 2.1404 mL | |
| 40 mM | 0.0642 mL | 0.3211 mL | 0.6421 mL | 1.6053 mL | |
| 50 mM | 0.0514 mL | 0.2569 mL | 0.5137 mL | 1.2843 mL | |
| 60 mM | 0.0428 mL | 0.2140 mL | 0.4281 mL | 1.0702 mL | |
| 80 mM | 0.0321 mL | 0.1605 mL | 0.3211 mL | 0.8027 mL |
GDC-3280 Related Classifications
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