| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
IC50: 2.8 nM (human PDE4)[1]
Lotamilast targets phosphodiesterase 4 (PDE4), an enzyme that catalyzes the hydrolysis of cyclic adenosine monophosphate (cAMP) to AMP. By inhibiting PDE4, lotamilast increases intracellular cAMP levels, which activates protein kinase A (PKA) and leads to the suppression of pro-inflammatory cytokine production in immune cells. This mechanism reduces inflammation and is the basis for its therapeutic potential in inflammatory skin diseases. |
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| ln Vitro |
Lotamilast decreases the production of several cytokines from human lymphocytes and monocytes with IC50 values ranging from 0.49 to 3.1 nM, and it potently and selectively inhibits human PDE4 activity with an IC50 of 2.8 nM[1].
In vitro, lotamilast potently and selectively inhibits human PDE4 activity with an IC50 of 2.8 nM. It inhibits the production of various cytokines in human lymphocytes and monocytes with IC50 values of 0.49-3.1 nM. The compound's ability to inhibit PDE4 and reduce cytokine production has been confirmed in various cell-based assays. Lotamilast shows selectivity for PDE4 over other PDE isoforms. |
| ln Vivo |
Phase 2 trials are presently being conducted on lotamilast for the treatment of mild-to-moderate atopic dermatitis. Topical administration of Lotamilast in mouse models results in both an immediate anti-inflammatory and anti-pruritic impact with decreased production of adhesion molecules and cytokines. Based on these results, topical RVT-501 shows inhibitory effects similar to tacrolimus in reducing the formation of skin lesions resembling atopic dermatitis in two types of AD models: hapten- and mite-elicited models[1]. In mice with chronic dermatitis, a single topical treatment of Lotamilast dramatically reduces spontaneous scratching within 1-2 hours of application; the inhibition is partial and ranges from 0.01% to 0.03%. Mice with chronic dermatitis show a significant reduction in the enhanced activity of the cutaneous nerve when 0.03% Lotamilast is applied topically to the rostral back. In mice with chronic dermatitis, there is a considerable drop in the cutaneous concentration of cAMP. This decline can be reversed by using topical Lotamilast [2].
In vivo, lotamilast has been developed for the treatment of inflammatory skin diseases such as atopic dermatitis. However, specific in vivo efficacy data in animal models are not extensively detailed in the available literature. The compound's potent PDE4 inhibition and anti-inflammatory effects suggest therapeutic potential in inflammatory conditions. Clinical studies have evaluated its safety and efficacy in atopic dermatitis. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for lotamilast are PDE4 inhibition assays using purified PDE4 enzyme. The enzyme is incubated with a cAMP substrate and varying concentrations of lotamilast, and the rate of cAMP hydrolysis is measured. The IC50 for inhibition of PDE4 activity is determined from dose-response curves. Selectivity is assessed by testing the compound against other PDE isoforms.
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| Cell Assay |
In vitro cellular assays for lotamilast are performed using human lymphocytes or monocytes. Cells are treated with varying concentrations of lotamilast and stimulated with inflammatory agents. Cytokine production (e.g., TNF-α, IL-4, IL-13) is measured by ELISA. Intracellular cAMP levels are measured using ELISA or FRET-based assays. Cell viability is evaluated using MTT assays to ensure that the observed effects are not due to cytotoxicity.
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| Animal Protocol |
In vivo animal experiments for lotamilast are conducted in animal models of inflammatory skin diseases, such as atopic dermatitis models in mice. Mice are sensitized and challenged with allergens, and lotamilast is applied topically or administered orally. Skin inflammation, epidermal thickness, and inflammatory cell infiltration are assessed. However, detailed protocols are not extensively documented in the available literature.
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| ADME/Pharmacokinetics |
Lotamilast has a molecular weight of 472.49 g/mol and a molecular formula of C26H24N4O5. It is a selective PDE4 inhibitor with an IC50 of 2.8 nM. The compound should be stored under recommended conditions. Detailed pharmacokinetic parameters such as half-life, Cmax, and bioavailability have been characterized in clinical studies. As a topical and systemic agent, lotamilast has been evaluated for dermatological applications.
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| Toxicity/Toxicokinetics |
Lotamilast has been evaluated in clinical studies and has been reported to be well-tolerated. Common adverse effects may include mild to moderate application site reactions, gastrointestinal disturbances, or headache. No significant safety concerns have been reported in clinical trials. Comprehensive safety data are available from clinical studies. The compound is a research tool and is not an approved drug.
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| References |
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| Additional Infomation |
E6005 has been used in trials investigating the treatment of atopic dermatitis.
Lotamilast is a selective phosphodiesterase 4 (PDE4) inhibitor with an IC50 of 2.8 nM. It is also known as RVT-501 and E6005. Lotamilast inhibits the production of various cytokines in human lymphocytes and monocytes with IC50 values of 0.49-3.1 nM. It has been developed for the treatment of inflammatory skin diseases such as atopic dermatitis. Lotamilast is a research compound with potential applications in inflammatory diseases. |
| Molecular Formula |
C26H24N4O5
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|---|---|
| Molecular Weight |
472.5
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| Exact Mass |
472.175
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| CAS # |
947620-48-6
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| Related CAS # |
947620-48-6;
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| PubChem CID |
24864553
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
3.889
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
35
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| Complexity |
716
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
BBTFKAOFCSOZMB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H24N4O5/c1-27-26-29-20-14-22(34-3)21(33-2)13-19(20)23(30-26)17-6-5-7-18(12-17)28-24(31)15-8-10-16(11-9-15)25(32)35-4/h5-14H,1-4H3,(H,28,31)(H,27,29,30)
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| Chemical Name |
methyl 4-((3-(6,7-dimethoxy-2-(methylamino)quinazolin-4-yl)phenyl)carbamoyl)benzoate
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| Synonyms |
E-6005 RVT501E6005 RVT 501 lotamilast E6005 RVT-501
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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 (~52.91 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.29 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1164 mL | 10.5820 mL | 21.1640 mL | |
| 5 mM | 0.4233 mL | 2.1164 mL | 4.2328 mL | |
| 10 mM | 0.2116 mL | 1.0582 mL | 2.1164 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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