| ln Vitro |
PDE3/4-IN-4 (compound D5) (10-60 μM; 24 hours) showed no significant toxicity to normal LO2 human hepatocytes after 24 hours of treatment at concentrations up to 60 μM [1]. PDE3/4-IN-4 (compound D5) inhibited IL-6 secretion in lipopolysaccharide (LPS)-stimulated LO2 cells with an IC50 value of 14.89 μM [1]. PDE3/4-IN-4 (compound D5) (15 μM; 12 hours of pretreatment before 4 hours of LPS stimulation) increased the expression of p-CREB and p-PKA in LPS-induced LO2 cells [1]. PDE3/4-IN-4 (compound D5) showed good metabolic stability in mouse, rat, dog, monkey, and human liver microsomes [1].
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|---|---|
| ln Vivo |
PDE3/4-IN-4 (compound D5) (10-40 mg/kg; orally; once daily; for 7 days) reduced liver inflammation and fibrosis in bile duct ligation (BDL) mice, with the 40 mg/kg dose showing the best effect [1]. PDE3/4-IN-4 (10-40 mg/kg; orally; once daily; for 7 days) reduced liver inflammation and damage in cecal ligation perforation (CLP) mice, with the 40 mg/kg dose showing the best effect [1].
|
| Cell Assay |
Western Blot Analysis [1]
Cell Types: LPS-induced LO2 cells Tested Concentrations: 15 μM (pretreatment before LPS stimulation) Incubation Duration: 12 hours (pretreatment 4 hours before LPS stimulation) Experimental Results: Compared with LPS-induced cells, the expression of phosphorylated CREB (p-CREB) and phosphorylated PKA (p-PKA) was significantly increased; the increase in p-CREB expression was confirmed by immunofluorescence staining. |
| Animal Protocol |
Animal/Disease Models:C57BL/6 (male, 18-22 g, bile duct ligation surgery) [1]
Doses: 10 mg/kg; 40 mg/kg Route of Administration: Oral; daily; 7 days Experimental Results: Significantly reduced hepatic IL-6 and IL-1β mRNA expression; reduced total bile acid (TBA) and alanine aminotransferase (ALT) levels; partially restored liver structure (HE staining); increased hepatic p-CREB and p-PKA expression; reduced collagen deposition (Masson staining, 40 mg/kg group only); the 40 mg/kg group showed better efficacy. Animal/Disease Models:C57BL/6 (male, 18-22 g, cecal ligation and puncture) [1] Doses: 10 mg/kg; 40 mg/kg Route of Administration: Oral; daily; 7 days Experimental Results: Reduced hepatic IL-6 and IL-1β mRNA expression; reduced total bile acid (TBA), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels; increased hepatic p-CREB and p-PKA expression; reduced hepatic inflammatory cell infiltration and restored hepatocyte structure (HE staining, 40 mg/kg group only); reduced collagen deposition (Masson staining, 40 mg/kg group only); the 40 mg/kg group had better efficacy. |
| References |
| Molecular Formula |
C30H27F2N5O4
|
|---|---|
| Molecular Weight |
559.56
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| CAS # |
3088024-27-2
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| Appearance |
Typically exists as solids at room temperature
|
| SMILES |
CC1CC(NN=C1C2=CC=C(C=C2)NC(C3=CC=CC4=C3N=C(N4)C5=CC(OCC6CC6)=C(C=C5)OC(F)F)=O)=O
|
| HS Tariff Code |
2934.99.9001
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 1.7871 mL | 8.9356 mL | 17.8712 mL | |
| 5 mM | 0.3574 mL | 1.7871 mL | 3.5742 mL | |
| 10 mM | 0.1787 mL | 0.8936 mL | 1.7871 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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