Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Cilomilast
- DrugBank Accession Number
- DB03849
- Background
Cilomilast (Ariflo, SB-207,499) is a drug which was developed for the treatment of respiratory disorders such as asthma and Chronic Obstructive Pulmonary Disease (COPD). It is orally active and acts as a selective Phosphodiesterase-4 inhibitor. Following four clinical trials, the drug proved to be effective in treating COPD, however it has never been marketed due to a poor side effect profile.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Cilomilast (DB03849)
- Weight
- Average: 343.4168
Monoisotopic: 343.178358293 - Chemical Formula
- C20H25NO4
- Synonyms
- Ariflo
- Cilomilast
- cis-4-cyano-4-(3-(cyclopentyloxy)-4-methoxyphenyl)cyclohexanecarboxylic acid
- External IDs
- SB 207499
- SB-207,499
- SB-207499
- SB207499
Pharmacology
- Indication
Investigated for use/treatment in chronic obstructive pulmonary disease (COPD).
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Not Available
- Mechanism of action
Cilomilast shows high selectivity for cAMP-specific PDE4, an isoenzyme that predominates in pro-inflammatory and immune cells and that is 10-fold more selective for PDE4D than for PDE4A, -B or -C. In vitro, cilomilast suppresses the activity of several pro-inflammatory and immune cells that have been implicated in the pathogenesis of asthma and COPD. Moreover, it is highly active in animal models of these diseases. Cilomilast has been shown to exert potent anti-inflammatory effects both in vitro and in vivo.
Target Actions Organism A3',5'-cyclic-AMP phosphodiesterase 4D inhibitorHumans A3',5'-cyclic-AMP phosphodiesterase 4A inhibitorHumans A3',5'-cyclic-AMP phosphodiesterase 4B inhibitorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareRiociguat Cilomilast may increase the hypotensive activities of Riociguat. - Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as anisoles. These are organic compounds containing a methoxybenzene or a derivative thereof.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Phenol ethers
- Sub Class
- Anisoles
- Direct Parent
- Anisoles
- Alternative Parents
- Phenoxy compounds / Methoxybenzenes / Alkyl aryl ethers / Nitriles / Monocarboxylic acids and derivatives / Carboxylic acids / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- Alkyl aryl ether / Anisole / Aromatic homomonocyclic compound / Carbonitrile / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Ether / Hydrocarbon derivative / Methoxybenzene
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 8ATB1C1R6X
- CAS number
- 153259-65-5
- InChI Key
- CFBUZOUXXHZCFB-OYOVHJISSA-N
- InChI
- InChI=1S/C20H25NO4/c1-24-17-7-6-15(12-18(17)25-16-4-2-3-5-16)20(13-21)10-8-14(9-11-20)19(22)23/h6-7,12,14,16H,2-5,8-11H2,1H3,(H,22,23)/t14-,20-
- IUPAC Name
- (1s,4s)-4-cyano-4-[3-(cyclopentyloxy)-4-methoxyphenyl]cyclohexane-1-carboxylic acid
- SMILES
- COC1=C(OC2CCCC2)C=C(C=C1)[C@]1(CC[C@@H](CC1)C(O)=O)C#N
References
- Synthesis Reference
Christensen, Siegfried B.; Guider, Aimee; Forster, Cornelia J.; Gleason, John G.; Bender, Paul E.; Karpinski, Joseph M.; Dewolf,, Walter E.; Barnette, Mary S.; et al. (1998). "1,4-Cyclohexanecarboxylates: Potent and Selective Inhibitors of Phosophodiesterase 4 for the Treatment of Asthma". Journal of Medicinal Chemistry 41 (6): 821–35.
- General References
- Torphy TJ, Barnette MS, Underwood DC, Griswold DE, Christensen SB, Murdoch RD, Nieman RB, Compton CH: Ariflo (SB 207499), a second generation phosphodiesterase 4 inhibitor for the treatment of asthma and COPD: from concept to clinic. Pulm Pharmacol Ther. 1999;12(2):131-5. [Article]
- Ochiai H, Ohtani T, Ishida A, Kusumi K, Kato M, Kohno H, Kishikawa K, Obata T, Nakai H, Toda M: Highly potent PDE4 inhibitors with therapeutic potential. Bioorg Med Chem Lett. 2004 Jan 5;14(1):207-10. [Article]
- External Links
- KEGG Drug
- D01704
- PubChem Compound
- 151170
- PubChem Substance
- 46505062
- ChemSpider
- 18826005
- BindingDB
- 50346088
- ChEMBL
- CHEMBL511115
- ZINC
- ZINC000100042108
- PDBe Ligand
- CIO
- Wikipedia
- Cilomilast
- PDB Entries
- 1xlx / 1xom
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data3 Completed Treatment Chronic Obstructive Pulmonary Disease (COPD) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0155 mg/mL ALOGPS logP 3.91 ALOGPS logP 3.9 Chemaxon logS -4.4 ALOGPS pKa (Strongest Acidic) 2.33 Chemaxon pKa (Strongest Basic) -4.6 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 79.55 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 93 m3·mol-1 Chemaxon Polarizability 37.25 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9742 Blood Brain Barrier + 0.8165 Caco-2 permeable + 0.5624 P-glycoprotein substrate Non-substrate 0.5848 P-glycoprotein inhibitor I Non-inhibitor 0.6738 P-glycoprotein inhibitor II Non-inhibitor 0.6658 Renal organic cation transporter Non-inhibitor 0.7946 CYP450 2C9 substrate Non-substrate 0.709 CYP450 2D6 substrate Non-substrate 0.8309 CYP450 3A4 substrate Substrate 0.6456 CYP450 1A2 substrate Non-inhibitor 0.5574 CYP450 2C9 inhibitor Non-inhibitor 0.5812 CYP450 2D6 inhibitor Non-inhibitor 0.9383 CYP450 2C19 inhibitor Non-inhibitor 0.5328 CYP450 3A4 inhibitor Non-inhibitor 0.6644 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7841 Ames test Non AMES toxic 0.8722 Carcinogenicity Non-carcinogens 0.9202 Biodegradation Not ready biodegradable 0.681 Rat acute toxicity 2.7220 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9728 hERG inhibition (predictor II) Non-inhibitor 0.7201
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-002f-0097000000-2ed324b8c509b1383353 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-0009000000-cad3dd51b6f187af7694 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0036-0094000000-19d65b1eea309b97c2c6 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0291000000-8d6e20c2a6290319d819 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0ff3-2392000000-6c1600da93161ead32be Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0pb9-4893000000-e952ad3ef7a1ce1e71cc Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 196.7132169 predictedDarkChem Lite v0.1.0 [M-H]- 172.2741 predictedDeepCCS 1.0 (2019) [M+H]+ 200.8758169 predictedDarkChem Lite v0.1.0 [M+H]+ 174.6321 predictedDeepCCS 1.0 (2019) [M+Na]+ 196.7199169 predictedDarkChem Lite v0.1.0 [M+Na]+ 181.26872 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes
- Specific Function
- 3',5'-cyclic-amp phosphodiesterase activity
- Gene Name
- PDE4D
- Uniprot ID
- Q08499
- Uniprot Name
- 3',5'-cyclic-AMP phosphodiesterase 4D
- Molecular Weight
- 91114.1 Da
References
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
- Kroegel C, Foerster M: Phosphodiesterase-4 inhibitors as a novel approach for the treatment of respiratory disease: cilomilast. Expert Opin Investig Drugs. 2007 Jan;16(1):109-24. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Hydrolyzes the second messenger 3',5'-cyclic AMP (cAMP), which is a key regulator of many important physiological processes
- Specific Function
- 3',5'-cyclic-amp phosphodiesterase activity
- Gene Name
- PDE4A
- Uniprot ID
- P27815
- Uniprot Name
- 3',5'-cyclic-AMP phosphodiesterase 4A
- Molecular Weight
- 98142.155 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes (PubMed:15260978). May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents
- Specific Function
- 3',5'-cyclic-amp phosphodiesterase activity
- Gene Name
- PDE4B
- Uniprot ID
- Q07343
- Uniprot Name
- 3',5'-cyclic-AMP phosphodiesterase 4B
- Molecular Weight
- 83342.695 Da
References
- Kroegel C, Foerster M: Phosphodiesterase-4 inhibitors as a novel approach for the treatment of respiratory disease: cilomilast. Expert Opin Investig Drugs. 2007 Jan;16(1):109-24. [Article]
Drug created at June 13, 2005 13:24 / Updated at August 26, 2024 19:22