YKS-34
YKS-34 is an orally active PDE4B inhibitor (IC50 = 1.71 nM). YKS-34 inhibits LPS-induced TNF-α release in PBMCs and TGF-β-induced fibroblast activation by reducing Cyclic AMP (cAMP) (HY-B1511) hydrolysis and elevating cAMP signaling. YKS-34 dose-dependently improves lung function and attenuates fibrotic remodeling in Bleomycin (HY-108345)-induced pulmonary fibrosis mouse models, and it accumulates in lung tissue, shows limited brain exposure, does not induce emetic episodes in beagles, and exhibits weak inhibition of the hERG channel. YKS-34 can be used for research on idiopathic pulmonary fibrosis.
For research use only. We do not sell to patients.
- Formula: C22H16DClF3N3O5S
- Molecular Weight:528.91
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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
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
PDE4B 1.71 nM (IC50) |
TNF-α 9.85 nM (IC50) |
kv11.1 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| PBMC | IC50 |
9.85 nM
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Inhibition of LPS-induced TNF-α release in human PBMCs incubated 1 hr with compound prior to 4 hrs LPS stimulation measured by ELISA.
Inhibition of LPS-induced TNF-α release in human PBMCs incubated 1 hr with compound prior to 4 hrs LPS stimulation measured by ELISA.
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acs.jmedchem.6c02578 |
| CHO | IC50 |
> 40.00 μM
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Inhibition of hERG K+ channel in hERG-CHO cells by automated patch-clamp with IC50 > 40.00 μM at maximum tested concentration 40.00 μM.
Inhibition of hERG K+ channel in hERG-CHO cells by automated patch-clamp with IC50 > 40.00 μM at maximum tested concentration 40.00 μM.
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acs.jmedchem.6c02578 |
In Vitro
YKS-34 (20 μM; 48 h) inhibits TGF-β-induced expression of α-SMA, COL1A1, and FN1 in MRC-5 human lung fibroblasts[1].
YKS-34 (0.16-40 μM) inhibits hERG channels in hERG-CHO cells with an IC50 > 40 μM[1].
YKS-34 (120 min) undergoes oxidative defluorination, mono-oxidation, and oxidation followed by hydrogenation in human, rat, and mouse liver microsomes, and its human and mouse metabolic profiles are comparable, with no major human-specific metabolites[1].
YKS-34 (10-20 μM) maintains MRC-5 cell viability in the MRC-5 cell viability assay[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 human embryonic lung fibroblasts
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Concentration:20 μM (YKS-34); 10 ng/mL (TGF-β)
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Incubation Time:48 h
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Result:Markedly suppressed the TGF-β-induced elevation of α-SMA, COL1A1, and FN1 by Western blot analysis.
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-t | AUCinf | Bioavailability | Clearance (CL) |
|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 10 mg/kg | i.v. | 1.01 h | 0.08 h | 10390 ng/mL | 6458 ng·h/mL | 6483 ng·h/mL | / | 26.1 mL/min/kg |
| Mice[1] | 10 mg/kg | p.o. | 2.83 h | 0.25 h | 1787 ng/mL | 2581 ng·h/mL | 2624 ng·h/mL | 44 % | / |
| Mice[1] | 40 mg/kg | p.o. | 2.01 h | 1.00 h | 3523 ng/mL | 14602 ng·h/mL | 14861 ng·h/mL | 57 % | / |
| Rat[1] | 10 mg/kg | i.v. | 0.66 h | 0.08 h | 16900 ng/mL | 11295 ng·h/mL | 11301 ng·h/mL | / | 14.8 mL/min/kg |
| Rat[1] | 20 mg/kg | p.o. | 2.43 h | 3.33 h | 1900 ng/mL | 5683 ng·h/mL | 6014 ng·h/mL | 25 (text: 25.2) % | / |
| Rat[1] | 20 mg/kg | p.o. | 3.01 h | 0.67 h | 1807 ng/mL | 6692 ng·h/mL | 7530 ng·h/mL | 30 (text: 29.6) % | / |
| Dog[1] | 2 mg/kg | i.v. | 3.97 h | 0.08 h | 14277 ng/mL | 18684 ng·h/mL | 18880 ng·h/mL | / | 2.07 mL/min/kg |
| Dog[1] | 10 mg/kg | p.o. | 2.71 h | 1.00 h | 12967 ng/mL | 98929 ng·h/mL | 99294 ng·h/mL | 106 (text: 105.9) % | / |
| Dog[1] | 2 mg/kg | i.v. | 3.97 h | 2.07 h | 14277 ng/mL | 18684 ng·h/mL | 18880 ng·h/mL | / | 0.46 mL/min/kg |
| Dog[1] | 10 mg/kg | p.o. | 2.71 h | 1.00 h | 12967 ng/mL | 98929 ng·h/mL | 99294 ng·h/mL | 105.9 % | / |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (female, 4-6 weeks old)[1]
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Dosage:3 mg/kg; 10 mg/kg; 30 mg/kg
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Administration:intragastric gavage; twice daily; days 8-15
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Result:In bleomycin-challenged mice, dose-dependently ameliorated pulmonary dysfunction, reducing the elevated Ers and increasing the decreased IC, FVC, Crs, and Cst.
At 30 mg/kg, pulmonary function was restored to near-normal levels.
Reduced hydroxyproline content and suppressed FN1 and COL1A1 protein expression.
Attenuated alveolar destruction, inflammatory infiltration, and fibrotic expansion on H&E staining, and produced a dose-dependent reduction in collagen deposition on Masson staining; fibrosis severity was quantified by Ashcroft scoring.
Application
1. This compound can be used as a tracer
2. This compound can be used as an internal standard for quantitative analysis by NMR, GC-MS, or LC-MS.
Chemical Information
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Molecular Weight 528.91
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Formula C22H16DClF3N3O5S
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SMILES
O=S1(C2=C(NC(C=C3F)=CC=C3CC(O)=O)N=C(C4=CC=C(OC(F)([2H])F)C(Cl)=C4)N=C2CCC1)=O
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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)
YKS-34 Related Classifications
HY-191389S Related Classifications
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Keywords
- YKS-34
- YKS34
- YKS 34
- Phosphodiesterase (PDE)
- TNF Receptor
- TGF-β Receptor
- Potassium Channel
- Tumor Necrosis Factor Receptor
- TNFR
- Transforming growth factor beta receptors
- KcsA
- PDE4B
- TGF-β
- TNF-α
- bleomycin
- cAMP hydrolysis
- fibroblast activation
- hERG channel
- idiopathic pulmonary fibrosis
- lung function
- pulmonary fibrosis
- Inhibitor
- inhibitor
- inhibit