| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
PDE4B 15 nM (IC50) PDE4D 1.7 μM (IC50)
PDE4B-IN-2 targets phosphodiesterase 4B (PDE4B), a key enzyme in the cAMP signaling pathway that hydrolyzes cyclic AMP to AMP. PDE4B is involved in inflammatory signaling pathways. The compound is a selective PDE4B inhibitor with an IC50 of 15 nM. It also inhibits PDE4D with an IC50 of 1.7 µM, demonstrating selectivity for PDE4B over PDE4D. By inhibiting PDE4B, the compound increases intracellular cAMP levels, which in turn suppresses pro-inflammatory cytokine production. PDE4B-IN-2 exhibits potent anti-inflammatory effects. |
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| ln Vitro |
No CYP1A2, CYP3A4, CYP2C9, or CYP2D is inhibited by PDE4B-IN-2 (compound 33) (IC50>10 µM)[1]. LPS-induced TNF-production in vitro from mouse peripheral blood mononuclear cells (PBMC; IC50=0.5 M) is inhibited by PDE4B-IN-2[1].
PDE4B-IN-2 demonstrates potent in vitro inhibition of PDE4B with an IC50 of 15 nM. It also inhibits PDE4D with an IC50 of 1.7 µM, demonstrating selectivity for PDE4B over PDE4D. The compound exhibits potent anti-inflammatory effects in vitro. By inhibiting PDE4B, the compound increases intracellular cAMP levels, suppressing pro-inflammatory cytokine production. These in vitro findings confirm the compound's selectivity and anti-inflammatory activity, supporting its potential for treating inflammatory diseases. |
| ln Vivo |
In mice, PDE4B-IN-2 (compound 33; 2 mg/kg; po) exhibits an AUC of 52.3 μg·h/mL and a Cmax of 8.7 μg/mL[1].
PDE4B-IN-2 is described as an orally active PDE4B inhibitor, indicating that it has sufficient oral bioavailability to exert effects in vivo. The compound exhibits potent anti-inflammatory effects, suggesting potential efficacy in animal models of inflammatory diseases. Further in vivo studies are needed to fully characterize the compound's efficacy, pharmacokinetics, and safety in animal models. PDE4B-IN-2 serves as a valuable tool for studying PDE4B-dependent inflammatory pathways and developing targeted anti-inflammatory therapies. |
| Enzyme Assay |
The in vitro enzyme assay for PDE4B-IN-2 involves measuring its inhibition of PDE4B and PDE4D enzymatic activities. Recombinant human PDE4B and PDE4D are expressed and purified. Enzyme activity is assessed by measuring the hydrolysis of cAMP to AMP using a scintillation proximity assay or fluorescence polarization. PDE4B-IN-2 is incubated with the enzyme and substrate at various concentrations. IC50 values are determined by fitting the inhibition data to a dose-response curve. The assay buffer typically contains Tris-HCl, MgCl2, and appropriate components for enzyme activity.
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| Cell Assay |
In vitro cellular assays for PDE4B-IN-2 typically use immune cells or cell lines to assess anti-inflammatory effects. Cells are treated with PDE4B-IN-2 at various concentrations and stimulated with pro-inflammatory stimuli such as LPS. Intracellular cAMP levels are measured using ELISA. Pro-inflammatory cytokine production (e.g., TNF-α, IL-6) is measured by ELISA or multiplex assays. The compound's ability to inhibit cytokine production is quantified. These assays confirm the compound's cellular activity and support its use in inflammatory disease research.
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| Animal Protocol |
In vivo animal experiments for PDE4B-IN-2 would typically use animal models of inflammatory diseases, such as LPS-induced endotoxemia or models of rheumatoid arthritis. As an orally active compound, PDE4B-IN-2 would be administered via oral gavage. Inflammatory markers in serum and tissues would be measured. Disease severity in models of chronic inflammation would be assessed. Pharmacodynamic studies could evaluate target engagement and pathway modulation. The compound's anti-inflammatory effects support its potential for treating inflammatory diseases.
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| ADME/Pharmacokinetics |
PDE4B-IN-2 is described as an orally active PDE4B inhibitor, indicating that it has sufficient oral bioavailability to exert effects in vivo. The compound has a molecular weight of 387.89, which is within the range typical for orally available small molecules. Its selectivity for PDE4B over PDE4D may influence its pharmacokinetic and pharmacodynamic profile. Further pharmacokinetic studies, including assessments of absorption, distribution, metabolism, and excretion (ADME), are necessary to fully characterize its PK profile.
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| Toxicity/Toxicokinetics |
Toxicological data for PDE4B-IN-2 are not extensively available in the public domain. As a research compound used for studying PDE4B inhibition, PDE4B-IN-2 has not undergone extensive toxicological evaluation. Standard cytotoxicity assays in cell lines may have been performed to assess safety margins. In animal studies, tolerability and potential adverse effects would be monitored. PDE4 inhibitors are known to have potential gastrointestinal side effects; the selectivity of PDE4B-IN-2 for PDE4B may help reduce such effects. Further preclinical toxicology studies would be required before clinical development.
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| References | |
| Additional Infomation |
4B phosphodiesterase inhibitors
PDE4B-IN-2 (A 33) is an orally active and selective PDE4B inhibitor with an IC50 of 15 nM. It inhibits PDE4D with an IC50 of 1.7 µM, demonstrating selectivity for PDE4B. The compound exhibits potent anti-inflammatory effects. It is designed to selectively inhibit PDE4B, an enzyme involved in cAMP breakdown. PDE4B-IN-2 has a molecular weight of 387.89. No clinical trials or regulatory approvals have been reported. It is available as a research-grade compound. |
| Molecular Formula |
C19H18CLN3O2S
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|---|---|
| Molecular Weight |
387.883121967316
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| Exact Mass |
387.08
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| CAS # |
915082-52-9
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| PubChem CID |
15951010
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| Appearance |
White to off-white solid powder
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| LogP |
5.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
26
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| Complexity |
476
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=CC=C(C2=NC(C)=C(CC)C(=N2)NC2C=CC(CC(=O)O)=CC=2)S1
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| InChi Key |
FDVSPBLZPJMXFV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H18ClN3O2S/c1-3-14-11(2)21-19(15-8-9-16(20)26-15)23-18(14)22-13-6-4-12(5-7-13)10-17(24)25/h4-9H,3,10H2,1-2H3,(H,24,25)(H,21,22,23)
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| Chemical Name |
2-[4-[[2-(5-chlorothiophen-2-yl)-5-ethyl-6-methylpyrimidin-4-yl]amino]phenyl]acetic acid
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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)
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| Solubility (In Vitro) |
DMSO: 25 mg/mL (64.45 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5781 mL | 12.8906 mL | 25.7812 mL | |
| 5 mM | 0.5156 mL | 2.5781 mL | 5.1562 mL | |
| 10 mM | 0.2578 mL | 1.2891 mL | 2.5781 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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