Chronic obstructive pulmonary disease

Disease ID:1187
Name:Chronic obstructive pulmonary disease
Associated with:0 target
42 immuno-relevant ligands
Description
Obstructive lung disease characterized by long-term poor airflow; includes chronic bronchitis and emphysema
Database Links
Disease Ontology: DOID:3083

Targets

No target related data available for Chronic obstructive pulmonary disease

Ligands

Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
salbutamol
Immuno Disease Comments: Used to treat bronchospasm due to COPD.
Clinical Use: Highly selective β2-adrenoceptor agonist used in the treatment of COPD and asthma.
In April 2015, the FDA expanded approval to include treatment or prevention of bronchospasm in patients with reversible obstructive airway disease and for the treatment of exercise-induced bronchospasm (EIB). | View clinical data
glycopyrrolate
Immuno Disease Comments: An anticholinergic bronchodilator used to treat asthma.
Clinical Use: Approved as an anticholinergic bronchodilator to relieve the symptoms of chronic obstructive pulmonary disease (COPD) [28] and asthma [12]. This drug may also be used pre-operatively to reduce salivary tracheobronchial and pharyngeal secretions and to reduce the acidity of gastric contents.
An inhalation formuation containing glycopyrrolate and (Utibron Neohaler®) was approved by the US FDA in November 2015 for the treatment of COPD.
In April 2016, the US FDA approved another fixed-dose inhalation aerosol formulation, glycopyrrolate plus the long-acting β agonist (LABA) (Bevespi Aerosphere®) for long-term, maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema.
In June 2018 the FDA approved glycopyrronium for the topical treatment (administered using a medicated cloth/wipe called Qbrexza®) of primary axillary hyperhidrosis. | View clinical data
Bioactivity Comments: Glycopyrrolate has high, equipotent affinity for all muscarinic acetylcholine receptor subtypes (M1-5) [27]. | View biological activity
abediterol
Immuno Disease Comments: No progress beyond Phase 2 trial (see NCT01425814).
Clinical Use: Phase 2a first-in-patient clinical trial results are published in [3]. The agent was generally well tolerated, producing a safe, potent, rapid and long-acting bronchodilatory effect in patients with persistent mild-to-moderate asthma. | View clinical data
Bioactivity Comments: Abediterol is functionally selective for β2-adrenoceptors over β1-adrenoceptors in cAMP production assays (showing 40-fold selectivity for β2 subtype receptors) [2]. In the same set of experiments showed over 500-fold selectivity for β2-adrenoceptors. | View biological activity
theophylline
Immuno Disease Comments: Approved drug for COPD.
Clinical Use: Used in the treatment of symptoms and reversible airways obstruction in conditions such as asthma, emphysema and chronic bronchitis. | View clinical data
salmeterol
Immuno Disease Comments: Used to treat bronchospasm due to COPD.
Clinical Use: Used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). Salmeterol is approved in a fixed-dose inhalation powder formulation with the long-acting β2-adrenergic agonist (AirDuo RespiClickTM) for the treatment of asthma. | View clinical data
MK-0359
Immuno Disease Comments: Completed Phase 2 clinical evaluation in COPD- see NCT00482235
Clinical Use: MK-0359 exhibited clinical efficacy in a Phase 2 study in asthma patients (NCT00482898), but caused gastrointestinal adverse effects [19]. It has completed Phase 2 studies in rheumatoid arthritis (NCT00482417) and chronic obstructive pulmonary disease (NCT00482235). | View clinical data
Bioactivity Comments: MK-0359 is active in vitro and in vivo [13]. It blocks LPS-induced TNF-α formation in whole blood assays with a potency similar to that exhibited by . Evidence suggest that majority of the anti-inflammatory effect of PDE4 inhibition is through PDE4B and PDE4D isozymes, and that PDE4D, as the major isoform in the brain responsible for emesis [24], is associated with the adverse gastrointestinal (GI) events associated with PDE4 inhibition. MK-0359 inhibits the hydrolysis of cAMP by PDE4A, 4B and 4D with similar potencies, which accounts for the adverse GI effects observed in clinical trial [19]. | View biological activity
ipratropium
Immuno Disease Comments: Bronchodilator used in treatment for bronchospasm in COPD.
Clinical Use: Used to treat bronchospasm associated with chronic obstructive pulmonary disease (COPD). | View clinical data
tiotropium
Immuno Disease Comments: Bronchodilator used in the treatment of COPD.
Clinical Use: A bronchodilator used in the treatment of chronic obstructuve pulmonary disease (COPD).
In May 2015 the US FDA approved a fixed-dose combination of tiotropium bromide and (Stiolto Respimat®) as 'a long-term, once-daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema' Drugs.com. Later in 2015, the FDA expanded approval to include tiotropium's use as a single agent (Spiriva Respimat®) as maintenance treatment of asthma in adults and adolescents. | View clinical data
prednisolone
Immuno Disease Comments: Glucocorticoid drug used to treat many inflammatory condtions including COPD.
Clinical Use: This drug used as an antiinflammatory or immunosuppressive agent and is indicated for the treatment of various inflammatory pathologies, including acute asthma, suppression of inflammatory and allergic disorders, ulcerative colitis, Crohn's disease, idiopathic thrombocytopenic purpura, rheumatoid arthritis, polymyalgia rheumatica, systemic lupus erythematosus and chronic obstructive pulmonary disease (COPD). | View clinical data
procaterol
Immuno Disease Comments: β2-adrenoceptor agonist approved outside of the EU and US for the treatment of COPD.
Clinical Use: Used in the treatment of asthma and chronic obstructive pulmonary disease. However, there is no information regarding approval for use of this drug on the US FDA or European Medicines Agency websites, although the compound does have an INN. Other national approval agencies may have granted marketing authorisation. See Drugs.com's International Drug Names list for futher information. | View clinical data
formoterol
Immuno Disease Comments: β2-adrenoceptor agonist approved for the treatment of COPD.
Clinical Use: Formoterol is used to manage the symptoms of asthma and/or chronic obstructive pulmonary disease (COPD). In November 2014, the EU EMA granted marketing authorisation of the fixed-dose combination medication Duaklir Genuair TM ( bromide/formoterol fumarate) as a maintenance bronchodilator for patients with COPD.
In April 2016, the US FDA approved the fixed-dose inhalation aerosol formulation, plus formoterol (Bevespi Aerosphere®) for long-term, maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema. | View clinical data
alvelestat
Immuno Disease Comments: A Phase 2 clinical candidate for COPD.
Clinical Use: A series of Phase I and Phase II results are reported in clinicaltrials.gov entries | View clinical data
Bioactivity Comments: In contrast with ONO6818, an inhibitor that binds covalently to NE, AZD9668 exhibited a more rapid association and dissociation rate, and its interaction with NE was fully reversible. It also generally showed greater specificity than ONO6818 or for NE over other neutrophil-derived serine proteases, particularly Pr-3 and pancreatic elastase [26]. Approximately 90 analogues are listed in a patent [1] where this is example 94, but only limited SAR data is included. | View biological activity
JNJ-10311795
Immuno Disease Comments: An experimental dual inhibitor of the leukocyte proteases cathepsin G and chymase with potential anti-inflammatory activity.
roflumilast
Immuno Disease Comments: A phosphodiesterase inhibitor approved to treat COPD.
Clinical Use: Roflumilast is used to treat asthma and chronic obstructive pulmonary disease (COPD) [14]. The drug reduces and prevents worsening of the lung inflammation that causes COPD.
Phase 1 proof-of-concept trials of topical roflumilast in patients with atopic dermatitis and psoriasis were withdrawn (apparently due to business decisions) before any participants were treated. | View clinical data
dyphylline
Immuno Disease Comments: A drug with bronchodilatory and vasodilatory actions that is used to manage the symptoms of COPD.
Clinical Use: Dyphylline is used to treat the symptoms of asthma, bronchitis, and emphysema. | View clinical data
Bioactivity Comments: We have been unable to find publicly available bioactivity data for this drug at its proposed molecular target(s) to substantiate its MMOA, and have therefore not tagged a primary drug target. | View biological activity
isoetarine
Immuno Disease Comments: A bronchodilator used to manage COPD.
Clinical Use: Used to treat emphysema, bronchitis, chronic obstructive pulmonary disease (COPD) and asthma. | View clinical data
Bioactivity Comments: The only publicly available bioactivity for this drug at its molecular target, β2-AR, resides in the PubChem bioassay data set, where an EC50 of 3840nM has been determined. | View biological activity
vilanterol
Immuno Disease Comments: A LABA used to treat COPD in combination with either a corticosteroid or anticholinergic drug.
Clinical Use: Vilanterol is contained in medications alongside a corticosteroid (eg furoate (PubChem CID 9854489 and vilanterol marketed as Breo Ellipta®) or an anticholinergic drug ( and vilanterol marketed as Anoro Ellipta®). Both of these medications were approved by the US FDA in 2013 to treat chronic obstructive pulmonary disease (COPD). In Europe, the EMA has approved Relvar Ellipta® (fluticasone furoate and vilanterol) for asthma and COPD. In May 2015, the US FDA expanded approval of Breo Ellipta® to include treatment of asthma. | View clinical data
umeclidinium
Immuno Disease Comments: An anticholinergic drug used as monotherapy or in combination wih the LABA vilanterol in COPD management.
Clinical Use: Umeclidinium is an anticholinergic drug, used in combination with as a combined single medication (marketed as Anoro Ellipta®) indicated for the treatment of chronic obstructive pulmonary disease (COPD) [9]. Umeclidinium is also available in a single agent medication called Incruse Ellipta®. | View clinical data
Bioactivity Comments: This compound has low nanomolar Kis for the M1 (0.16nM), M2 (0.15nM) and M3 (0.06nM) muscarinic acetylcholine receptor subtypes [17]. | View biological activity
cilomilast
Immuno Disease Comments: Clinical candidate for COPD (see Phase 3 NCT00103922).
Clinical Use: Cilomilast is being investigated for the treatment of conditions such as chronic obstructive pulmonary disease (COPD), bronchopulmonary dysplasia and asthma. ClinicalTrials.gov lists one completed trial for this compound (NCT00103922) | View clinical data
Bioactivity Comments: Cilomilast inhibits phosphodiesterase-4 (PDE4) with an IC50 of 120nM [10] | View biological activity
budesonide
Immuno Disease Comments: A glucocorticoid (corticosteroid) drug used to treat COPD.
Clinical Use: Used by inhalation to treat asthma and severe chronic obstructive pulmonary disease (COPD). EMA approvals (2014) are for products containing budesonide and formoterol. May be used to treat Crohn's disease (inflammatory bowel disease) [18], inflammatory skin disorders, allergic rhinitis and in an extended release formulation, ulcerative colitis [11]. Symbicort® inhalers contain a fixed-dose formualtion of budesonide and the β2-adrenoceptor bronchodilator .
Oral formulations of this drug have EMA orphan disease approval to treat graft-versus-host disease (2006) and eosinophilic oesophagitis (2013).
In October 2014, the US FDA approved a rectal foam formulation containing budesonide (Uceris®) for the treatment of ulcerative colitis. | View clinical data
indacaterol
Immuno Disease Comments: A LABA used to treat COPD, alone or in combination with glycopyrrolate.
Clinical Use: Indacaterol is a very long-acting, rapid onset β2-adrenoceptor agonist [5] approved for the once-daily management of asthma and chronic obstructive pulmonary disease (COPD).
A fixed-dose inhalation combination medicine containing incadaterol and (Utibron Neohaler) was approved by the US FDA in November 2015 for the treatment of COPD | View clinical data
arformoterol
Immuno Disease Comments: A LABA used to treat COPD.
Clinical Use: Arformoterol is indicated for the treatment of chronic obstructive pulmonary disease (COPD) and asthma. | View clinical data
AZ11657312 (salt free)
Immuno Disease Comments: Experimental compound.
Bioactivity Comments: Note that bioactivity will be associated with the hydrochloride salt. Pending publication, the data presented here is derived from the compound's record in AstaZeneca's Open Innovation Pharmacology Toolbox | View biological activity
dilmapimod
Immuno Disease Comments: Phase 2 candidate for COPD, but has not progressed further.
Clinical Use: SB-681323 has been assessed to Phase II in clinical trial for indications including chronic obstructive pulmonary disease, rheumatoid arthritis and neuropathic pain, although there are no currently active trials (as of Nov 2014). Click here to view the list of completed SB-681323 trials at ClinicalTrials.gov. | View clinical data
PH-797804
Immuno Disease Comments: Phase 2 candidate for COPD, but has not progressed further.
Clinical Use: PH-797804 has completed Phase 2 clinical trials for several inflammatory conditions, including rheumatoid and osteoarthritis, chronic obstructive pulmonary disease (COPD) [20] as well as PH-797804 vs. placebo for neuropathic pain associated with post-herpetic neuralgia. Click here to link to ClinicalTrials.gov's list of these completed trials. There are no currently active trials assessing PH-797804 (March 2016). | View clinical data
AZD2423
Immuno Disease Comments: Failed Phase 2 clinical evaluation in COPD.
Clinical Use: AZD2423 was developed for neuropathic pain and chronic obstructive pulmonary disease (COPD), but failed Phase II clinical trials. Click here to link to ClinicalTrials.gov's full listing of trials assessing AZD2423. Phase II trials can be accessed by clicking here. | View clinical data
AZD9056
Immuno Disease Comments: Developed with potential for treating COPD, but development was discontinued.
Clinical Use: AZD9056 was developed for the treatment of inflammatory conditions such as rheumatoid arthritis (RA), chronic obstructive pulmonary disease (COPD) and Crohn’s disease. Phase II trial NCT00520572 for RA has been completed. There are no active trials in progress (Nov 2014). | View clinical data
Bioactivity Comments: The NIH National Center for Advancing Translational Sciences (NCATS) record for AZD9056 provides bioactivity data as follows: The IC50 for AZD9056-induced inhibition of pro-inflammatory IL-1β and IL-18 release from human peripheral monocytes is 10-13nM. | View biological activity
losmapimod
Immuno Disease Comments: Phase 2 trials in COPD have been completed (see NCT01218126 for example).
Clinical Use: Losmapimod is being assessed in Phase II clinical trial for chronic obstructive pulmonary disease (COPD; NCT01541852) and focal segmental glomerulosclerosis (FSGS; NCT02000440). A Phase III clinical outcomes study in patients with acute coronary syndrome (ACS) is underway (NCT02145468). | View clinical data
AZD1236
Immuno Disease Comments: Phase 2 candidate for COPD, but has not progressed further.
Clinical Use: A Phase IIa study evaluated the effects of AZD1236 on the biomarkers of inflammation and emphysematous lung tissue degradation in patients with moderate-to-severe COPD [6]. No clinical efficacy was demonstrated but evidence of an impact on desmosine suggests potential value in longer-term treatment of COPD. | View clinical data
PF-03715455
Immuno Disease Comments: Designed as an inhalation drug for the treatment of COPD.
Bioactivity Comments: In cells, PF-03715455 action on p38α translates into potent inhibition of the release of proinflammatory cytokines relevant to COPD [21]. Potential cross over targets are reported as p38β and misshapen-like kinase 1 (MINK) [21]. | View biological activity
amelubant
Immuno Disease Comments: No progress in development beyond Phase 2 trial in COPD.
Clinical Use: Amelubant (BIIL 284) reached Phase 2 clinical trial for inflammatory conditions including chronic obstructive pulmonary disease (COPD), bronchial asthma and rheumatoid arthritis (RA). | View clinical data
Bioactivity Comments: As a prodrug, amebulant has very little affinity for the BLT1 receptor [4]. Bioactivity is attributed to its active metabolite, . | View biological activity
example 131 [WO2009133348]
Immuno Disease Comments: A compound developed with predicted clinical utility in COPD.
Bioactivity Comments: Example 131 is inactive against other trypsin-like serine proteases (plasma kallikrein, thrombin, trypsin and plasmin) [8]. | View biological activity
navarixin
Immuno Disease Comments: Clinical trials in COPD were terminated.
Clinical Use: Navarixin (SCH-527123) has been evaluated in Phase II clinical trials for immune conditions such as allergen-induced asthma, chronic obstructive pulmonary disease (COPD) and psoriasis. | View clinical data
elubirixin
Immuno Disease Comments: No progress in development beyond Phase 1.
Clinical Use: SB-656933 has been evaluated in Phase II clinical trial aiming to reduce neutrophil-mediated airway inflammation in cystic fibrosis patients (NCT00903201 [22]), and in Phase I trials as a potential treatment for chronic obstructive pulmonary disease (COPD). | View clinical data
danirixin
Immuno Disease Comments: Phase 2 clinical candidate for COPD (see NCT03034967).
Clinical Use: Danirixin is being evaluated in Phase II clinical trials as a potential anti-inflammatory treatment for the neutrophil-mediated airway inflammation associated with chronic obstructive pulmonary disease (COPD) and influenza Infection. | View clinical data
bimosiamose
Immuno Disease Comments: No progress beyond Phase 2 trial.
Clinical Use: Bimosiamose has completed Phase II clinical trials in patients with chronic obstructive pulmonary disease (COPD; inhaled bimosiamose, NCT01108913 [29]) and psoriasis (topically applied bimosiamose, NCT00823693) | View clinical data
Bioactivity Comments: We do not include the selectins as molecular targets in this database.
Bimosiamose (TBC1269) has a reported IC50 of 70μM in a P-selectin HL-60 cell assay [16]. | View biological activity
acumapimod
Immuno Disease Comments: Phase 2 clinical candidate for COPD (see NCT02700919).
Clinical Use: Acumapimod is being evaluated in Phase 2 clinical trial (NCT02700919) for the treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). | View clinical data
rosiptor
Immuno Disease Comments: Phase 3 clinical candidate for COPD.
Clinical Use: AQX-1125 has reached Phase 2 clinical trial in chronic inflammatory conditions such as unstable chronic obstructive pulmonary disease (COPD) and atopic dermatitis, and Phase 3 for interstitial cystitis/bladder pain syndrome [23] (see NCT02858453). Click here to link to ClinicalTrials.gov's full list of AQX-1125 trials. | View clinical data
Bioactivity Comments: AQX-1125 activates INPP5D enzyme activity by 20% (reducing the KM from 214 (control) to 180 [25]. This reduction in KM is concentration-dependent, but the compound has no effect on the enzyme's turnover constant (kcat) or maximum velocity (Vmax), which is indicative of allosteric modulation [25]. | View biological activity
TG6-129
Immuno Disease Comments: Probe compound for experimental use.
nemiralisib 7
Immuno Disease Comments: Phase 2 clinical candidate for COPD (see NCT02522299).
Clinical Use: Nemiralisib (as GSK2269557) is in Phase 2 clinical development. Two separate studies are underway in patients with chronic obstructive pulmonary disease (COPD; NCT02522299) or the rare genetic condition activated PI3K-delta syndrome (APDS/PASLI; NCT02593539). | View clinical data
Bioactivity Comments: Nemiralisib (GSK2269557) inhibits IFNγ production in vitro and protects against eosinophil recruitment in a relevant brown Norway rat acute OVA model of Th2 driven lung inflammation. The compund is reported to be >1000-fold selective for PI3Kδ over all of the kinases (>250) in the Millipore kinase panel and has low/acceptable hERG liability. | View biological activity
PF-06263276
Immuno Disease Comments: Predicted to offer clinical anti-inflammatory effects in COPD.
Clinical Use: PF-06263276 was progressed to clinical trial and has completed Phase 1 evaluation in subjects with plaque psoriasis (NCT02193815), although this was only a 12 day study. | View clinical data
Bioactivity Comments: In vitro and in vivo potencies, and the pharmacokinetic and safety profiles of PF-06263276 indicate suitability for inhaled or topical therapy to treat inflammatory diseases, such as COPD or psoriasis, through direct administration to the lungs or skin, thus avoiding any systemic effects of JAK inhibition [15]. IC50 evaluation was performed at 100nM ATP. | View biological activity
andecaliximab
Immuno Disease Comments: Phase 1 study in COPD (NCT02077465) has been completed.
Clinical Use: Andecaliximab (GS-5745) is being evaluated in various clinical trials (max Phase 3) for cancers and inflammatory conditions. Click here to link to all of the trials registered with ClinicalTrials.gov. Trials in ulcerative colitis and Crohn's disease were terminated early (2016) due to meeting pre-specified futility and efficacy criteria in an interim analysis of unblinded efficacy and safety data. A Phase 2 study in rheumatoid arthritis has also been terminated. Evaluation for anti-cancer efficacy appears to be ongoing. Phase 2 trial NCT02864381 is evaluating andecaliximab in combination with the anti-PD-1 checkpoint inhibitor in unresectable or recurrent gastric or gastroesophageal junction adenocarcinoma. | View clinical data

References

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