| Size | Price | Stock | Qty |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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Purity: ≥98%
Roflumilast (BY-217; APTA-2217; B 9302-107; BYK20869; Daxas; Daliresp) is a novel, highly potent, selective, and long-acting inhibitor of phosphodiesterase 4/PDE4 with potential anti-inflammatory activity. It inhibits PDE4 with IC50s of 0.2-4.3 nM in a cell-free assay. It has anti-inflammatory effects and is under development as an orally administered drug for the treatment of inflammatory conditions of the lungs such as asthma, and chronic obstructive pulmonary disease (COPD). In vitro studies show that roflumilast inhibits the production of inflammatory mediators in a variety of human immune cells, suggesting a role for reducing COPD-related inflammation.
| ln Vitro |
Roflumilast is a subnanomolar inhibitor of the majority of PDE4 splice variants tested and has no effect on PDE enzymes other than PDE4. With the exception of PDE4C (4C1, IC50=3 nM; 4C2, IC50= 4.3 nM), which is inhibited with somewhat lesser potency, it does not demonstrate PDE4 isoform selectivity [2]. A strong and specific PDE4 inhibitor is roflumast. At concentrations up to 10,000-fold, roflumilast does not affect other PDE isoenzymes, such as PDE1, PDE2, PDE3, or PDE5. This makes it a monoselective inhibitor of PDE4. Roflumilast inhibits the activity of human neutrophils. Roflumilast prevents monocyte-derived dendritic cells from synthesizing TNFα. Cytokine synthesis and CD4+ T cell proliferation are inhibited by rolfumilast. Up to 60% of proliferation can be inhibited by rolumilast at a potency (IC30) of 7 nM [3].
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| ln Vivo |
Studies on animals using roflumilast have demonstrated that it decreases the build-up of neutrophils in bronchoalveolar lavage fluid following short-term tobacco smoke exposure in mice, rats, or guinea pigs; additionally, it eliminates the infiltration of inflammatory cells in the lung parenchyma of rats exposed to tobacco smoke for seven months [2]. In pIgR, rolumilast prevents the advancement of COPD?*? rats. 9-month-old WT or pIgR for these investigations?*? For three months, mice received oral gavage treatment with either 100 μg of Roflumilast (5 μg/g) or a vehicle (4% methylcellulose, 1.3% PEG400). Around the age of 12 months, the lungs were taken. When Roflumilast was administered to mice, minor airway wall remodeling did not advance as it did in vehicle-treated pIgR-/- animals. Surprisingly, pIgR aged 12 months who received rolumilast?*? Compared to 9-month-old pIgR, mice's emphysema index was lower.*? Roflumilast not only stops pulmonary emphysema from developing in this scenario, as demonstrated by the mice. appears to aid in the resolution of the emphysematous loss of lung parenchyma throughout the course of emphysema [4].
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| Animal Protocol |
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
After a 500mcg dose, the bioavailability of roflumilast is about 80%. In the fasted state, maximum plasma concentrations are reached in 0.5 to 2 hours, while in the fed state, Cmax is reduced by 40%, Tmax is increased by one hour, and total absorption is unchanged. Applied topically, the mean systemic exposure for roflumilast and its N-oxide metabolite in adults was 72.7 ± 53.1 and 628 ± 648 h∙ng/mL, respectively. The mean systemic exposure for roflumilast and its N-oxide metabolite in adolescents was 25.1 ± 24.0 and 140 ± 179 h∙ng/mL, respectively. Roflumilast is excreted 70% in the urine as roflumilast N-oxide. Following a single oral dose of 500 mcg, the volume of distribution of roflumilast is approximately 2.9 L/kg. Plasma clearance of roflumilast following short-term intravenous infusion is approximately 9.6 L/h. Metabolism / Metabolites Roflumilast is metabolized to roflumilast N-oxide, the active metabolite of roflumilast in humans, by CYP3A4 and CYP1A2. The N-oxide metabolite is less potent than its parent drug in regards to PDE4 inhibition, but its plasma AUC is approximately 10-fold greater. Biological Half-Life Following oral administration, the plasma half-lives of roflumilast and roflumilast N-oxide are 17 hours and 30 hours, respectively. |
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| Toxicity/Toxicokinetics |
Hepatotoxicity
In preregistration studies, roflumilast was not associated with serum enzyme elevations or with episodes of clinically apparent liver injury. Since approval of roflumilast, there have been no published reports of hepatotoxicity, and the product label does not mention liver injury as an adverse event. Likelihood score: E (unlikely cause of clinically apparent liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the use of roflumilast in nursing mothers. The drug and its metabolite are more than 97% bound to plasma proteins, so amounts in milk are likely to be very low. However, the manufacturer and some experts recommend that the oral drug should not be used by women who are nursing. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding Plasma protein binding of roflumilast and its N-oxide metabolite is approximately 99% and 97%, respectively. |
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| References |
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| Additional Infomation |
Pharmacodynamics
Roflumilast and its active metabolite, roflumilast N-oxide, increase cyclic adenosine-3′, 5′-monophosphate (cAMP) in affected cells by inhibiting PDE4. They are highly selective for PDE4 and are effectively inactive against PDEs 1, 2, 3, 5, and 7. |
| Molecular Formula |
C17H14CL2F2N2O3
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|---|---|
| Molecular Weight |
403.2075
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| Exact Mass |
402.034
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| CAS # |
162401-32-3
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| Related CAS # |
Roflumilast N-oxide;292135-78-5;Roflumilast-d4 N-Oxide;1794760-31-8;Roflumilast Impurity E;1391052-76-8;Roflumilast-d4;1398065-69-4;Roflumilast-d3;1189992-00-4
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| PubChem CID |
449193
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
430.6±45.0 °C at 760 mmHg
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| Melting Point |
158°C
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| Flash Point |
214.2±28.7 °C
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| Vapour Pressure |
0.0±1.0 mmHg at 25°C
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| Index of Refraction |
1.604
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| LogP |
4.84
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
26
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| Complexity |
475
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
MNDBXUUTURYVHR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H14Cl2F2N2O3/c18-11-6-22-7-12(19)15(11)23-16(24)10-3-4-13(26-17(20)21)14(5-10)25-8-9-1-2-9/h3-7,9,17H,1-2,8H2,(H,22,23,24)
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| Chemical Name |
3-(cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)benzamide
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| Synonyms |
Daliresp; BY217; BY-217; B 9302-107;BYK 20869;B-9302-107;APTA 2217, B9302-107, BY 217, BYK-20869; BYK20869; Daxas;
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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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.20 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
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 corn oil and mix evenly. Solubility in Formulation 2: 30% PEG400+0.5% Tween80+5% propylene glycol:30 mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4801 mL | 12.4005 mL | 24.8010 mL | |
| 5 mM | 0.4960 mL | 2.4801 mL | 4.9602 mL | |
| 10 mM | 0.2480 mL | 1.2400 mL | 2.4801 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05684744 | Completed | Drug: Roflumilast Drug: Methotrexate |
Psoriasis | Cairo University | January 9, 2023 | Phase 2 Phase 3 |
| NCT04322929 | Recruiting | Drug: Roflumilast Oral Tablet | Non-cystic Fibrosis Bronchiectasis | The University of Hong Kong | November 12, 2020 | Phase 2 |
| NCT04549870 | Completed | Drug: Roflumilast | Psoriasis | Bispebjerg Hospital | January 1, 2021 | Phase 2 |
| NCT04108377 | Terminated | Drug: Roflumilast Drug: Placebo |
Asthma | University of California, Davis | January 21, 2019 | Phase 1 |
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