Phosphodiesterase-IN-5
Phosphodiesterase-IN-5 is a potent, orally active and selective phosphodiesterase 10A (PDE10A) inhibitor with an IC50 of 6.2 nM. Phosphodiesterase-IN-5 shows >1612-fold selectivity over other PDEs. Phosphodiesterase-IN-5 exhibits potent antifibrotic efficacy in a Bleomycin (BLM) (HY-108345)-induced murine model of pulmonary fibrosis (PF) by blocking myofibroblast differentiation via the cAMP/PKA/CREB signaling pathway. Phosphodiesterase-IN-5 can be used for the research of PF.
For research use only. We do not sell to patients.
- Formula: C26H26FN7O
- Molecular Weight:471.53
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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PDE10A 6.2 nM (IC50) |
Phosphodiesterase-IN-5 (compound QC-3) (5-20 μM; 48 h) exhibits antifibrotic activity in TGF-β1 (HY-163536)-stimulated MRC-5 cells via activation of the cAMP/PKA/CREB pathway, which inhibits myofibroblast differentiation and ECM deposition[1].
Phosphodiesterase-IN-5 binds the catalytic domain of PDE10A, forming hydrogen bonds with Gln726 and hydrophobic interactions with Ile692, while the 6-F substituent enables halogen bonding with Asp674 via a water molecule[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MRC-5 cells
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Concentration:3.125, 6.25, 12.5, 25, 50, 100, 200 μM
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Incubation Time:48 h
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Result:Showed no cytotoxic in MRC-5 cells at concentrations up to 200 μM.
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Cell Line:TGF-β1-stimulated MRC-5 cells
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Concentration:5, 10, 20 μM
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Incubation Time:48 h
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Result:Demonstrated concentration-dependent reductions in FN, COL-I, and α-SMA protein expression.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male C57BL/6 mice (7-9 weeks old, 20-24 g) induced by BLM[1]
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Dosage:2.5, 5, 10 mg/kg
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Administration:i.g.; daily for 21 days
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Result:Dose-dependently reversed BLM-induced changes in Penh, endexpiratory pause (EEP), relaxation time (RT), andfrequency (f), nearly restoring them to normal levels.
Mitigated BLM-induced body weight loss and elevated lung coefficient in a dose-dependent manner.
Reduced IL-6 and TGF-β levels in broncho alveolar lavage fluid (BALF), and restored pulmonary cAMP levels.
Markedly reduced BLM-induced increases in IL-6 and TGF-β levels in BALF, with the mos pronounced inhibition observed at the 10 mg/kg dose.
Restored pulmonary cAMP levels.
Improved pulmonary morphology.
Effectively reduced the level of alveolar wall thickening, inflammatory cell infiltration, and collagen deposition.
Showed a dose-dependent reduction in fibrotic lesions.
Significantly suppressed the BLM- induced overexpression of fibrotic markers such as FN, COL-I, and α-SMA, with the most pronounced effect observed at a dose of 10 mg/kg.
Chemical Information
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Molecular Weight 471.53
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Formula C26H26FN7O
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SMILES
O=C(C1=C(C2CN(C3=NC(C)=C4C=CC=CC4=N3)C2)N=C5C=CC(F)=CN51)N(C6)CCNC76CC7
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Zhang F, et al. Structure-Based Optimization of Imidazopyridine Derivatives as Selective and Orally Bioavailable Phosphodiesterase 10A Inhibitors with Reduced Blood-Brain Barrier Penetration for the Treatment of Idiopathic Pulmonary Fibrosis. J Med Chem. 2025;68(23):25290-25306. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Phosphodiesterase-IN-5 Related Classifications
HY-179645 Related Classifications
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