PDE4B/D-IN-5
PDE4B/D-IN-5 (Compound P32) is a peripherally restricted, oral active inhibitor of PDE4B and PDE4D with extremely low blood-brain barrier penetration, with IC50 values of 3.4 nM and 2.2 nM, respectively. PDE4B-IN-8 inhibits the production of TNF-α. PDE4B/D-IN-5 significantly reduces the Bax/Bcl2 ratio, and alleviates oxidative stress by decreasing MPO activity and NO levels. PDE4B/D-IN-5 exhibits anti-inflammatory, antioxidant, and anti-apoptotic activities. PDE4B/D-IN-5 can be used for the research of acute lung injury.
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- CAS No.: 3064814-26-9
- Formule: C22H21F2N5O2
- Masse moléculaire:425.43
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
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PDE4B1 3.4 nM (IC50) |
PDE4D3 2.2 nM (IC50) |
PDE4B/D-IN-5 potently inhibits recombinant PDE4B1 in an in vitro fluorescence polarization enzyme activity assay (IC50 = 3.4 nM)[1].
PDE4B/D-IN-5 (15 μM; up to 90 min) exhibits high metabolic stability in rat liver microsomes, with 94.8% remaining after 60 min, a half-life of 5.5 h, and a clearance as low as 0.0021 mL min−1 mg−1[1].
PDE4B/D-IN-5 (1-4 μM; 1 h) dose-dependently inhibits LPS-stimulated TNF-α production in RAW264.7 mouse macrophages[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:RAW264.7 murine macrophages
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Concentration:1-4 μM
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Incubation Time:1 h
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Result:Reduced supernatant TNF-α levels in a dose-dependent manner compared to the LPS-induced model group (which had TNF-α levels of 26 pg/mL, vs baseline 9 pg/mL in untreated cells).
| Species | Dose | Route | Tmax | Cmax | AUC0-t | AUC0-∞ | T1/2 | MRT |
|---|---|---|---|---|---|---|---|---|
| Mice[1] | 1 (plasma) mg/kg | i.v. | 4.98 min | 7665.53 ng/mL | 5661.94 ng·h/mL | 5735.78 ng·h/mL | 1.26 h | 1.09 h |
| Mice[1] | 25 (plasma) mg/kg | p.o. | 36 min | 46941.22 ng/mL | 111577.48 ng·h/mL | 127646.89 ng·h/mL | 2.45 h | 3.40 h |
| Mice[1] | 1 (brain) mg/kg | i.v. | 9.98 min | 49.69 ng/mL | 73.90 ng·h/mL | 80.96 ng·h/mL | 2.07 h | 2.71 h |
PDE4B/D-IN-5 (6-12 mg/kg; i.p.; daily; 5 days) dose-dependently attenuates LPS-induced acute lung injury in male C57BL/6 mice via anti-inflammatory, antioxidant, and antiapoptotic effects mediated by the cAMP-Epac pathway[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 mice (male, 8 weeks old, acute lung injury model via intratracheal LPS instillation)[1]
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Dosage:6 mg/kg; 12 mg/kg
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Administration:i.p.; daily; 5 days
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Result:Reduced lung erythema, enlargement, alveolar damage, interstitial edema, and inflammatory cell infiltration.
Showed a significant reduction in Smith lung injury scores in the 12 mg/kg group compared to the model group.
Reduced lung wet/dry weight ratios with a dose-dependent trend.
Reduced bronchoalveolar lavage fluid (BALF) neutrophil counts more effectively than dexamethasone, with a dose-dependent effect.
Attenuated lung myeloperoxidase (MPO) activity more potently than dexamethasone, with a dose-dependent effect.
Reduced lung tissue nitric oxide (NO) levels to values comparable to dexamethasone.
Suppressed BALF tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) levels in a dose-dependent manner, with the 12 mg/kg group showing greater suppression than dexamethasone.
Dose-dependently elevated lung tissue cAMP levels, with the 12 mg/kg group showing the most pronounced effect.
Induced a dose-dependent, significant upregulation of Epac1 protein expression.
Significantly decreased the Bax/Bcl2 ratio, indicating suppression of mitochondrial apoptosis.
Showed no statistically significant changes in p-PKA/PKA or p-AMPK/AMPK ratios.
Chemical Information
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CAS No. 3064814-26-9
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Masse moléculaire 425.43
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Formule C22H21F2N5O2
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SMILES
FC([H])(CN1N=C(C2=CC=NN2CC)C3=C1C=CC(NC4=CC=C(CC(O)=O)C=C4)=C3)F
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PDE4B/D-IN-5 Related Classifications
HY-182060 Related Classifications
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