Investigational Drug Details
| Drug ID: | D307 |
| Drug Name: | Roflumilast |
| Synonyms: | -- |
| Type: | Chemical drug |
| DrugBank ID: | DB01656 |
| DrugBank Description: | Roflumilast is a phosphodiesterase-4 (PDE-4) inhibitor. Due to its selective inhibition of the PDE4 isoenzyme in lung cells, roflumilast is indicated for the management of chronic obstrtuctive pulmonary disease (COPD) exacerbations. Treatment with Roflumilast is associated with an increase in psychiatric adverse reactions, including suicide and suicidal attempts. |
| PubChem ID: | 449193 |
| CasNo: | 162401-32-3 |
| Repositioning for NAFLD: | Yes |
| SMILES: | O(CC1CC1)c1c(OC(F)F)ccc(c1)C(=O)Nc1c(Cl)cncc1Cl |
| Structure: |
|
| InChiKey: | MNDBXUUTURYVHR-UHFFFAOYSA-N |
| Molecular Weight: | 403.212 |
| DrugBank Targets: | cAMP-specific 3',5'-cyclic phosphodiesterase 4D inhibitor; cAMP-specific 3',5'-cyclic phosphodiesterase 4A inhibitor; cAMP-specific 3',5'-cyclic phosphodiesterase 4B inhibitor; cAMP-specific 3',5'-cyclic phosphodiesterase 4C inhibitor |
| DrugBank MoA: | Roflumilast is a phosphodiesterase-4 (PDE-4) inhibitor which, due to its selective inhibition of the PDE4 isoenzyme, has potential antiinflammatory and antimodulatory effects in the pulmonary system. It is thought that the increased levels of intracellular cyclic AMP are responsible for the therapeutic actions of Roflumilast. |
| DrugBank Pharmacology: | Roflumilast (and its active metabolite, roflumilast N-oxide) increases cyclic adenosine-3′, 5′-monophosphate (cAMP) in lung cells by inhibiting PDE4. Increased cAMP activates PKA, which inactivates transcription factors involved in inflammation. Romflumilast also decreases the amount of sputum neutrophils and eosinophils in COPD patients. |
| DrugBank Indication: | Roflumilast is indicated as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. Roflumilast is not a bronchodilator and is not indicated for the relief of acute bronchospasm. |
| Targets: | PDE4C inhibitor; PDE4B inhibitor; Pde4 inhibitor; PDE4A inhibitor; PDE4D inhibitor |
| Therapeutic Category: | Antiasthmatic drug |
| Clinical Trial Progress: | Phase 2 terminated (NCT01703260: Company decision; No safety or efficacy concerns.) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted | |
|---|---|---|---|---|---|---|---|
| L0929 | NCT01703260 | Phase 2 | Not recruiting | Has Results | 02/10/2012 | 19 October 2017 | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A01216 | 34826603 | Pharmacol Res | Overexpression of PDE4D in mouse liver is sufficient to trigger NAFLD and hypertension in a CD36-TGF-β1 pathway: therapeutic role of roflumilast. | Details |
| A17196 | 27917591 | Diabetes Obes Metab | The PDE4 inhibitor roflumilast reduces weight gain by increasing energy expenditure and leads to improved glucose metabolism. | Details |