PDE/TRPA1/CHIT1-IN-1
PDE/TRPA1/CHIT1-IN-1 is a phosphodiesterases (PDEs), TRPA1, and hCHIT1 (KD of 37.7 μM) inhibitor. PDE/TRPA1/CHIT1-IN-1 is a broad-spectrum PDE inhibitor, potently targeting key isoforms including PDE4B, PDE7A, PDE3A, and PDE8A with IC50s of 15.54, 15.15, 8.39 and 16.46 μM. PDE/TRPA1/CHIT1-IN-1 suppresses NLRP3 inflammasome activation and inhibits NF-κB phosphorylation, downregulating the expression of pro-inflammatory genes (TNF-α and IL-6) in vivo. PDE/TRPA1/CHIT1-IN-1 can be used for chronic obstructive pulmonary disease (COPD) and related inflammatory lung disorders research.
For research use only. We do not sell to patients.
- Formula: C28H33N7O5
- Molecular Weight:547.61
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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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PDE4B 15.54 μM (IC50) |
PDE7A 15.15 μM (IC50) |
PDE3A 8.39 μM (IC50) |
PDE8A 16.64 μM (IC50) |
PDE1B 54.47 μM (IC50) |
PDE2A 79.61 μM (IC50) |
PDE4D 130.50 μM (IC50) |
PDE5A 26.86 μM (IC50) |
PDE10A 36.13 μM (IC50) |
PDE/TRPA1/CHIT1-IN-1 (compound 39) (10 μM, 1 h) possesses anti-inflammatory activity in Lipopolysaccharides (LPS) (HY-D1056)-stimulated RAW264.7 macrophages[1].
PDE/TRPA1/CHIT1-IN-1 inhibits PDE1B, PDE2A, PDE4B, PED7A, PDE3A, PDE4D, PDE5A, PDE8A and PDE10A with IC50s of 54.47, 79.61, 15.54, 15.15, 8.39, 130.50, 26.86, 16.46 and 36.13 μM, respectively[1].
PDE/TRPA1/CHIT1-IN-1 (1-50 μM, 1 h) inhibits bronchial smooth muscle cell (BSMC) hyperplasia and hypertrophy, reduces extracellular matrix (ECM) component secretion in both BSMC and human lung fibroblast cell line (MRC-5) cells, and inhibits the fibroblast-to-myofibroblast transition[1].
PDE/TRPA1/CHIT1-IN-1 shows bronchorelaxant effects with IC50 values of 1.56 μM, and maximal relaxation of precontracted tracheal segments with the maximal relaxation of 100 % in rat tracheal segments[1].
PDE/TRPA1/CHIT1-IN-1 possesses high metabolic stability (t₁/₂ = 53.42 min, Clint = 32.43 μL/min/mg), negligible hepatocytotoxicity (IC50 = 34.70 μM in HepG2 cells), and medium membrane permeability (logPe = -5.305)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:LPS-stimulated RAW264.7 macrophages
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Concentration:10 μM
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Incubation Time:1 h
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Result:Caused an almost twofold reduction in TNF-α and IL-6 levels in LPS-induced RAW264.7 cells, lowering TNF-α concentrations to 381.74 pg/mL and decreasing IL-6 concentrations to 141.02 pg/mL.
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Cell Line:FBS induced-MRC-5, FBS induced-BSMC, TGF-β induced- MRC-5 and TGF-β induced-BSMC
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Concentration:1, 10 and 50 μM
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Incubation Time:1 h
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Result:Reduced BSMC and MRC-5 proliferation by 38 % and 32 % at a concentration of 10 μM.
Reduced TGF-β-induced expression of COL1A1 and FN1 genes in both cell lines.
Decreased TGF-β-induced ACTA2 expression in BSMCs by almost a 3-fold.
Reduce TGF-β-induced ACTA2 expression in lung fibroblasts.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:PPE (HY-B2118) (intranasally,i.n. once a week for 4 week) induced-Balb/c male mice (8-10 weeks, 23-25 g)[1]
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Dosage:25 mg/kg
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Administration:i.p., once daily; for 2 weeks
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Result:Protected against elastase-induced emphysema with a mean linear intercept (MLI) values of 50.36 μM.
Ameliorated the elastase-induced increase in total inflammatory cells in in bronchoalveolar lavage fluid (BALF).
Reduced the total number of all inflammatory cells in BALF collected from the PPE-induced model.
Acted as a relatively strong inhibitor of PDE7A and PDE3A, as well as a TRPA1 antagonist.
Reduced the PPE-induced transcript levels of key inflammatory genes in lung homogenates to control levels.
Decrease in Tnfa, Cxcl2, Il6, and Il1b expression.
Limited the levels of NLRP3 inflammasome components and consequently reduced the activation of NLRP3 inflammasome components.
Reduced the PPE-induced level of cleaved caspase-1, which may have inhibited the formation of interleukin 1β (IL-1β), a hallmark cytokine of NLRP3 inflammasome activation.
Reduced NF-κB phosphorylation, as well as the expression of various proinflammatory genes, including Tnfa, Cxcl2, Il6, and Il1b.
Chemical Information
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Molecular Weight 547.61
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Formula C28H33N7O5
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SMILES
O=C(OC(C)(C)C)C1=CC=C(NC(CCCN2C(NCC3=NC=CC=C3)=NC(N(C)C(N4C)=O)=C2C4=O)=O)C=C1
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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
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PDE/TRPA1/CHIT1-IN-1 Related Classifications
HY-179503 Related Classifications
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