roflumilast   Click here for help

GtoPdb Ligand ID: 6962

Synonyms: ARQ-151 (roflumilast cream) | BY-217 | BYK-20869 | Daliresp® | Daxas®
Approved drug PDB Ligand Immunopharmacology Ligand
roflumilast is an approved drug (EMA (2010), FDA (2011))
Compound class: Synthetic organic
Comment: Roflumilast is a phosphodiesterase-4 inhibitor.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 3
Hydrogen bond donors 1
Rotatable bonds 8
Topological polar surface area 60.45
Molecular weight 402.03
XLogP 4
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES FC(Oc1ccc(cc1OCC1CC1)C(=O)Nc1c(Cl)cncc1Cl)F
Isomeric SMILES FC(Oc1ccc(cc1OCC1CC1)C(=O)Nc1c(Cl)cncc1Cl)F
InChI 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)
InChI Key MNDBXUUTURYVHR-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
Oral roflumilast is used to treat asthma and chronic obstructive pulmonary disease (COPD) [1]. The drug reduces and prevents worsening of the lung inflammation that causes COPD.
AstraZeneca's proof-of-concept trials of topical roflumilast in patients with atopic dermatitis and psoriasis were withdrawn, for business reasons, before any participants were treated. In a licensing agreement with AstraZeneca, evaluation of topical roflumilast for dermatological inflammatory conditions has been resumed by Arcutis Biotherapeutics, who have both a roflumilast cream (ARQ-151) and roflumilast foam (ARQ-154) in clinical development. The most advanced is Phase 3 ARQ-151 for plaque psoriasis [2].
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Upon inhibition of phosphodiesterase-4, cAMP levels in lung cells increase in turn activating protein kinase A. This leads to inactivation of transcription factors involved in the inflammation underlying COPD.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03638258 The Safety, Efficacy and Pharmacokinetics of ARQ-151 Cream in Subjects With Chronic Plaque Psoriasis Phase 2 Interventional Arcutis Biotherapeutics, Inc. Six weeks of once daily roflumilast cream was superior to placebo in efficacy to clear or almost clear psoriatic lesions. Based on these positive results Arcutis Biotherapeutics have advanced topical roflumilast to Phase 3. 2
NCT04286607 Open-Label Extension Trial of PDE4 Inhibition With Roflumilast for the Management of Plaque Psoriasis Phase 3 Interventional Arcutis Biotherapeutics, Inc.
NCT04211363 Trial of PDE4 Inhibition With Roflumilast for the Management of Plaque Psoriasis Phase 3 Interventional Arcutis Biotherapeutics, Inc.
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