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Purity: ≥98%
Lotamilast (formerly RVT-501; E-6005) is a novel, potent and selective inhibitor of phosphodiesterase 4 (PDE-4, IC50 = 2.8 nM) with the potential to be used for the treatment of AD/atopic dermatitis. It suppresses the production of various cytokines from human lymphocytes and monocytes with IC50 of 0.49-3.1 nM; produces an immediate antipruritic effect as well as an anti-inflammatory effect with reduced expression of cytokines/adhesion molecules in mice after topical application; ameliorates the appearance of atopic dermatitis-like skin lesions in AD models.
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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].
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| 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].
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| References |
[1]. Ishii N, et al. Antipruritic effect of the topical phosphodiesterase 4 inhibitor E6005 ameliorates skin lesions in a mouse atopic dermatitis model. J Pharmacol Exp Ther. 2013 Jul;346(1):105-12.
[2]. Andoh T, et al. Topical E6005, a novel phosphodiesterase 4 inhibitor, attenuates spontaneous itch-related responses in mice with chronic atopy-like dermatitis. Exp Dermatol. 2014 May;23(5):359-61 |
| Molecular Formula |
C26H24N4O5
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| Molecular Weight |
472.5
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| Exact Mass |
472.1747
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| CAS # |
947620-48-6
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| Related CAS # |
947620-48-6;
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| SMILES |
O=C(OC)C1=CC=C(C(NC2=CC=CC(C3=C4C=C(OC)C(OC)=CC4=NC(NC)=N3)=C2)=O)C=C1
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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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| 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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