| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg | |||
| Other Sizes |
| Targets |
PDE4B .94 μM (IC50)
The primary target of PDE4B-IN-3 is the phosphodiesterase 4B (PDE4B) enzyme. It acts as an antagonist, directly binding to the enzyme's active site with an IC50 of 0.94 microM. This inhibition prevents the hydrolysis of cAMP, thereby prolonging and enhancing its intracellular signaling. |
|---|---|
| ln Vitro |
PDE4B-IN-3 (compound f4), with IC50 values of 20.40 μM, 23.48 μM, and 18.98 μM in RAW264.7 cells, exhibits strong inhibitory activity on the generation of NO, TNF-α, and IL-1β. In RAW264.7 cells, PDE4B-IN-3 may also suppress the expression of COX-2 and iNOS[1].
In non-cellular enzyme assays, PDE4B-IN-3 demonstrates potent inhibition with an IC50 of 0.94 microM. In cell-based assays using RAW264.7 macrophages, PDE4B-IN-3 effectively suppresses the production of key pro-inflammatory mediators. It inhibits NO, TNF-alpha, and IL-1beta production with IC50 values of 20.40 microM, 23.48 microM, and 18.98 microM, respectively. |
| ln Vivo |
PDE4B-IN-3 (compound f4; 10–30 mg/kg) has been shown in vivo studies to reduce serum levels of inflammatory components TNF-α and IL-1β in a dose-dependent manner and to ameliorate the degree of knee joint pathology and foot swelling in adjuvant-induced arthritic rats[1].
In vivo studies in a rat model of adjuvant-induced arthritis show that PDE4B-IN-3 is anti-inflammatory. Treatment with PDE4B-IN-3 at doses of 10-30 mg/kg significantly improves knee joint pathology and reduces foot swelling in a dose-dependent manner. It also dose-dependently decreases the serum levels of the inflammatory cytokines TNF-alpha and IL-1beta. |
| Enzyme Assay |
The non-cellular protocol for PDE4B-IN-3 is a standard PDE activity assay. Recombinant PDE4B enzyme is incubated with 3H-cAMP and varying concentrations of the inhibitor in a reaction buffer for 30 minutes at 37degC. The reaction is stopped by boiling, and 5'-nucleotidase is added to convert any remaining AMP to adenosine. The mixture is then applied to an ion-exchange resin, and the eluted radioactivity is measured.
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| Cell Assay |
To measure cellular anti-inflammatory activity, RAW264.7 cells are plated and treated with PDE4B-IN-3 at various concentrations (e.g., 1-100 microM). One hour later, cells are stimulated with 1 microg/mL lipopolysaccharide (LPS) to induce inflammation. After 18-24 hours, the culture supernatant is collected. The levels of TNF-alpha, IL-1beta, and NO are then measured using ELISA or Griess reagent kits.
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| Animal Protocol |
An in vivo protocol for PDE4B-IN-3 uses the adjuvant-induced arthritis model in male Sprague-Dawley rats. Adjuvant is injected into the left hind paw on day 0. Starting on day 15, rats are treated with PDE4B-IN-3 (10 or 30 mg/kg) daily via intraperitoneal injection. Paw volume is measured every 3-4 days using plethysmometry. On day 27, serum is collected for cytokine analysis, and knee joints are collected for histopathological assessment.
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| ADME/Pharmacokinetics |
Specific PK parameters for PDE4B-IN-3 are not detailed. However, the fact that significant in vivo anti-inflammatory effects are observed following intraperitoneal administration indicates that the compound is systemically bioavailable via this route. Further studies would be required to characterize its absorption, distribution, metabolism, and excretion.
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| Toxicity/Toxicokinetics |
Toxicological data for PDE4B-IN-3 is not provided. In the in vivo study described, the doses of 10 and 30 mg/kg were tolerated by the animals, as no significant adverse effects on body weight or overall health were reported, but specific toxicological endpoints were not the focus of the arthritis study.
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| References | |
| Additional Infomation |
PDE4B-IN-3 is a selective research tool for investigating the therapeutic potential of PDE4B inhibition in inflammatory diseases. The PDE4 family has four subtypes (A-D), and selective inhibition of the B subtype is of interest because it may offer anti-inflammatory benefits with fewer side effects, such as nausea and emesis, which are associated with non-selective PDE4 inhibitors.
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| Molecular Formula |
C30H35N3O4S2
|
|---|---|
| Molecular Weight |
565.75
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| Exact Mass |
565.207
|
| CAS # |
2819779-01-4
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| PubChem CID |
164517083
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
9
|
| Heavy Atom Count |
39
|
| Complexity |
984
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC(C)C1=CC(=C(C(=C1)C(C)C)S(=O)(=O)NC2=CC=CC(=C2)NS(=O)(=O)C3=CC=CC4=C3N=CC=C4)C(C)C
|
| InChi Key |
KNCHLPMJSHBPHC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C30H35N3O4S2/c1-19(2)23-16-26(20(3)4)30(27(17-23)21(5)6)39(36,37)33-25-13-8-12-24(18-25)32-38(34,35)28-14-7-10-22-11-9-15-31-29(22)28/h7-21,32-33H,1-6H3
|
| Chemical Name |
N-[3-[[2,4,6-tri(propan-2-yl)phenyl]sulfonylamino]phenyl]quinoline-8-sulfonamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: 50 mg/mL (88.38 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.42 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (4.42 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7676 mL | 8.8378 mL | 17.6757 mL | |
| 5 mM | 0.3535 mL | 1.7676 mL | 3.5351 mL | |
| 10 mM | 0.1768 mL | 0.8838 mL | 1.7676 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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