roflumilast   Click here for help

GtoPdb Ligand ID: 6962

Synonyms: ARQ-151/Zoryve® (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.
Click here for help

Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

✖

View interactive charts of activity data across species

IUPHAR Pharmacology Education Project (PEP) logo

View more information in the IUPHAR Pharmacology Education Project: roflumilast

roflumilast is commercially available from our sponsors

2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
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
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

✖
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.
External links Click here for help
For extended ADME data see the following:

Electronic Medicines Compendium (eMC)
Drugs.com
European Medicines Agency (EMA)