| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Lirimilast targets the enzyme phosphodiesterase 4 (PDE4), which is responsible for the hydrolysis of cyclic adenosine monophosphate (cAMP). By inhibiting PDE4, lirimilast increases intracellular cAMP levels. Elevated cAMP activates protein kinase A (PKA), which in turn inhibits the activity of various inflammatory cells, including T cells, macrophages, neutrophils, and eosinophils.
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| ln Vitro |
In PDE4 assays employing freshly produced PDE4 from human PMNL, Lirimilast (BAY 19-8004) was reported to be five times more powerful than Cilomilast and equivalent to CDP-840 [1].
In vitro, lirimilast inhibits PDE4 activity with high potency. It reduces the production of pro-inflammatory cytokines (e.g., TNF-α, IL-4, IL-5) from activated immune cells. It also suppresses the proliferation of T lymphocytes and the release of reactive oxygen species from neutrophils. Its anti-inflammatory effects are consistent with its mechanism as a PDE4 inhibitor. |
| ln Vivo |
Lirimilast (BAY 19-8004) seems to have strong therapeutic efficacy because it works well when given orally at 3 mg/kg in guinea pigs and, more significantly, at 0.1 mg/kg/day in primates. Furthermore, it was discovered that lyrilast was three times more powerful than cilomilast in a rat lung neutrophilic inflammation model [2].
In vivo, lirimilast has been studied in animal models of asthma and COPD. In ovalbumin-sensitized mice, it reduces airway hyperresponsiveness, eosinophilic infiltration, and mucus production in the lungs. It has also been shown to reduce inflammation in models of chronic bronchitis and pulmonary fibrosis. However, its clinical development may have been limited by side effects. |
| Enzyme Assay |
The in vitro enzyme inhibition assay for lirimilast involves measuring the activity of PDE4 in the presence of the compound. PDE4 is incubated with its substrate, cAMP, and the amount of cAMP hydrolyzed is measured. The IC50 of lirimilast is determined by plotting the percent inhibition of PDE4 activity against the concentration of the compound.
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| Cell Assay |
In vitro cellular assays for lirimilast are performed on immune cells such as peripheral blood mononuclear cells (PBMCs) or purified T cells. Cells are stimulated with a mitogen (e.g., phytohemagglutinin, PHA) or a specific antigen in the presence of lirimilast. The production of cytokines (e.g., TNF-α, IL-2) in the supernatant is measured by ELISA to assess its immunosuppressive effect.
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| Animal Protocol |
In vivo animal experiments for lirimilast were conducted in models of respiratory inflammation. The ovalbumin-induced asthma model in mice was used to evaluate its effect on airway inflammation. Lirimilast was typically administered orally or intraperitoneally, and parameters such as inflammatory cell counts in bronchoalveolar lavage fluid (BALF), cytokine levels, and airway resistance were measured.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic properties of lirimilast are not extensively documented in the available literature. As a small molecule with a molecular weight of 369.44 g/mol, it is expected to be well-absorbed after oral administration and to have reasonable bioavailability. PDE4 inhibitors typically have moderate to high protein binding and are metabolized in the liver.
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| Toxicity/Toxicokinetics |
Lirimilast, like other PDE4 inhibitors, is associated with a significant side effect profile. The most common side effects are gastrointestinal, including nausea, vomiting, and diarrhea, which are thought to be related to the role of PDE4 in the central nervous system. Other side effects can include headache, dizziness, and weight loss. These side effects have limited the clinical utility of many PDE4 inhibitors.
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| References |
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| Additional Infomation |
Lirimilast is one of several PDE4 inhibitors that were developed for the treatment of inflammatory diseases. While it showed promise in preclinical studies, it may not have progressed to late-stage clinical trials, possibly due to the side effect profile common to this class of drugs. Other PDE4 inhibitors, such as roflumilast, have been approved for COPD, while others, like apremilast, are used for psoriasis and psoriatic arthritis.
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| Molecular Formula |
C17H12N2O6SCL2
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|---|---|
| Molecular Weight |
443.25798
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| Exact Mass |
441.979
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| CAS # |
329306-27-6
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| PubChem CID |
6433118
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| Appearance |
White to off-white solid powder
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| Density |
1.619g/cm3
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| Boiling Point |
663.2ºC at 760 mmHg
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| Flash Point |
354.9ºC
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| Index of Refraction |
1.677
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| LogP |
5.467
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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 |
5
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| Heavy Atom Count |
28
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| Complexity |
715
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
YPFLFUJKZDAXRA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H12Cl2N2O6S/c1-28(24,25)27-9-3-5-11-13(7-9)26-16(14(11)21-17(20)23)15(22)10-4-2-8(18)6-12(10)19/h2-7H,1H3,(H3,20,21,23)
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| Chemical Name |
[3-(carbamoylamino)-2-(2,4-dichlorobenzoyl)-1-benzofuran-6-yl] methanesulfonate
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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 : ~100 mg/mL (~225.60 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 | 2.2560 mL | 11.2801 mL | 22.5601 mL | |
| 5 mM | 0.4512 mL | 2.2560 mL | 4.5120 mL | |
| 10 mM | 0.2256 mL | 1.1280 mL | 2.2560 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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