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Chronic obstructive pulmonary disease

GtoPdb Disease Summaries

This section gives an overview of the disease, and where available shows the following:

  • Synonyms: Shows known synonyms for the disease.
  • Description: Gives a basic description/definition of the disease.
  • Database Link: External links to the same disease at the Disease Ontology, OMIM or Orphanet sites.
  • Immunopharmacology comments: General comments about the target's role in immunopharmacology, provided by GtoImmuPdb curators.
  • Associated with: Counts are displayed for the total targets the disease is associated with in GtoPdb. The counts of targets and ligands of immunological relevance associated to the disease are also shown.

More information can be found in the help pages.

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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

GtoPdb Disease Summaries - Targets

Click on the target name to link to its detailed view page

Where available, information is display on the role of the target in the disease; drugs which target the disease and their therapeutic use and side-effects.

If there is mutation data curated in GtoPdb this is indicated, with a link back to the appropriate section on the target detailed view page

Immuno ligand interactions - If available, a table of immuno-relevant ligands is shown. These ligands have been curated as having an association to the disease and possess interaction data with the target in GtoPdb. The approval status of the ligand is shown, along with curator comments and an indication of whether the target is considered the primary target of the ligand.

More information can be found in the help pages.

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Key to terms and symbols

No target related data available for Chronic obstructive pulmonary disease

Ligands

GtoPdb Disease Summaries - Ligands

Click ligand name to view ligand summary page

  • Approved: If the ligand is an approved drug this is indicated, along with approval bodies.
  • Immuno: Immuno icon indicates the ligand is immuno-relevant

Click the arrow in the final column to expand comments

  • Immuno Disease Comments: Curatorial comments specifically added as part of GtoImmuPdb. They give more information on the association between the ligand and disease in the context of immunopharmacology.
  • Clinical Use: General clinical comments relating to the ligand and may not necessarily be specific to the disease in question. With hyperlink to more details on the ligand summary pages.
  • Bioactivty Comments: Curatorial comments specifically about the compounds biological activity - with hyperlink to more details on the ligand summary pages.

More information can be found in the help pages.

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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).
A first-in-class, fixed-dose combination asthma rescue medication (delivered by a pressurised metered-dose inhaler) containing salbutamol/albuterol and (an anti-inflammatory inhaled corticosteroid), Airsupra®, was approved by the FDA in 2023. | 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) [35] 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) [34]. | 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: As a monotherapy FDA and EMA approvals are for as the use of salmeterol xinafoate. Salmeterol xinafoate is indicated for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Salmeterol is also approved in a fixed-dose inhalation powder formulation with the long-acting β2-adrenergic agonist (e.g. AirDuo RespiClickTM or Aerivio SpiromaxTM) for the treatment of severe asthma and COPD. | 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 [22]. 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 [30], 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 [22]. | 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 1 and Phase 2 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 [33]. 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: Oral 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.
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 [20]. | 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 [18]. | 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) [21], inflammatory skin disorders, allergic rhinitis and in an extended release formulation, ulcerative colitis [11]. Symbicort® inhalers contain a fixed-dose formulation of budesonide and the β2-adrenoceptor bronchodilator .
Oral formulations of this drug were granted EMA orphan disease approval to treat graft-versus-host disease (2006) and eosinophilic oesophagitis (2013). Takeda's oral solution formulation of budesonide (Eohilia®, TAK-721) was FDA approved for the treatment for eosinophilic oesophagitis in February 2024.
In October 2014, the US FDA approved a rectal foam formulation containing budesonide (Uceris®) for the treatment of ulcerative colitis. In the EU, EMA approval for Stada Arzneimittel's micronised budesonide formulation (Kinpeygo, as orally administered capsules), for the treatment of primary immunoglobulin A nephropathy, was issued in 2022. | 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 2 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) [23] 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 2 clinical trials [16] and further development was discontinued. Click here to link to ClinicalTrials.gov's full listing of trials assessing AZD2423. | 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 2 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 has been evaluated in clinical trials for cardiovascular disease [28], inflammatory conditions and a muscle wasting disease [29,31]. It has failed to provide significant efficacy in trials for cardiovascular disease, and has failed to meet the primary endpoint in a Phase 2 facioscapulohumeral muscular dystrophy (FSHD) study (NCT04264442). | View clinical data
AZD1236
Immuno Disease Comments: Phase 2 candidate for COPD, but has not progressed further.
Clinical Use: A Phase 2a 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 [24]. Potential cross over targets are reported as p38β and misshapen-like kinase 1 (MINK) [24]. | 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 a number of Phase 2 clinical trials for immune conditions such as allergen-induced asthma, chronic obstructive pulmonary disease (COPD) and psoriasis. Development for these indications appears to have been discontinued. As of January 2019 the only active trial involving navarixin is NCT03473925, a Phase 2 study looking for efficacy of navarixin plus in a selected range of advanced/metastatic solid tumours. | View clinical data
elubirixin
Immuno Disease Comments: No progress in development beyond Phase 1.
Clinical Use: SB-656933 was evaluated in Phase 2 clinical trial aiming to reduce neutrophil-mediated airway inflammation in cystic fibrosis patients (NCT00903201 [26]), and Phase 1 for chronic obstructive pulmonary disease (COPD; ). A Phase 2 study in ulcerative colitis patiients (NCT00748410) was terminated. | View clinical data
danirixin
Immuno Disease Comments: Phase 2 clinical candidate for COPD (see NCT03034967).
Clinical Use: Danirixin is being evaluated in Phase 2 clinical trials as a potential anti-inflammatory treatment for the neutrophil-mediated airway inflammation associated with chronic obstructive pulmonary disease (COPD) [19]. Click here to link to ClinicalTrials.gov's full list of danirixin trials. | View clinical data
Bioactivity Comments: The pharmacokinetics and pharmacodynamics of danirixin in healthy subjects were reported in 2017 [25]. | View biological activity
bimosiamose
Immuno Disease Comments: No progress beyond Phase 2 trial.
Clinical Use: Bimosiamose has completed Phase 2 clinical trials in patients with chronic obstructive pulmonary disease (COPD; inhaled bimosiamose, NCT01108913 [36]) 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 [17]. | View biological activity
TG6-129
Immuno Disease Comments: Probe compound for experimental use.
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 [27] (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 [32]. 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 [32]. | View biological activity
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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1. Andersson, Marjana et al.. (2007) 2-Pyridone Derivatives As Neutrophil Elastase Inhibitors And Their Use. Patent number: US20070203129. Assignee: AstraZeneca. Priority date: 15/09/2004. Publication date: 30/08/2007.

2. Aparici M, Gómez-Angelats M, Vilella D, Otal R, Carcasona C, Viñals M, Ramos I, Gavaldà A, De Alba J, Gras J et al.. (2012) Pharmacological characterization of abediterol, a novel inhaled β(2)-adrenoceptor agonist with long duration of action and a favorable safety profile in preclinical models. J Pharmacol Exp Ther, 342 (2): 497-509. [PMID:22588259]

3. Beier J, Fuhr R, Massana E, Jiménez E, Seoane B, de Miquel G, Ruiz S. (2014) Abediterol (LAS100977), a novel long-acting β2-agonist: efficacy, safety and tolerability in persistent asthma. Respir Med, 108 (10): 1424-9. [PMID:25256258]

4. Birke FW, Meade CJ, Anderskewitz R, Speck GA, Jennewein HM. (2001) In vitro and in vivo pharmacological characterization of BIIL 284, a novel and potent leukotriene B(4) receptor antagonist. J Pharmacol Exp Ther, 297 (1): 458-66. [PMID:11259574]

5. Cazzola M, Matera MG, Lötvall J. (2005) Ultra long-acting beta 2-agonists in development for asthma and chronic obstructive pulmonary disease. Expert Opin Investig Drugs, 14 (7): 775-83. [PMID:16022567]

6. Dahl R, Titlestad I, Lindqvist A, Wielders P, Wray H, Wang M, Samuelsson V, Mo J, Holt A. (2012) Effects of an oral MMP-9 and -12 inhibitor, AZD1236, on biomarkers in moderate/severe COPD: a randomised controlled trial. Pulm Pharmacol Ther, 25 (2): 169-77. [PMID:22306193]

7. Down K, Amour A, Baldwin IR, Cooper AW, Deakin AM, Felton LM, Guntrip SB, Hardy C, Harrison ZA, Jones KL et al.. (2015) Optimization of Novel Indazoles as Highly Potent and Selective Inhibitors of Phosphoinositide 3-Kinase δ for the Treatment of Respiratory Disease. J Med Chem, 58 (18): 7381-99. [PMID:26301626]

8. Evans DM, Allan CE, Horton J, Rooker DP. (2009) Aminopyridine derivatives. Patent number: WO2009133348. Assignee: Vantia Limited.. Priority date: 29/04/2008. Publication date: 05/11/2009.

9. Feldman GJ, Edin A. (2013) The combination of umeclidinium bromide and vilanterol in the management of chronic obstructive pulmonary disease: current evidence and future prospects. Ther Adv Respir Dis, 7 (6): 311-9. [PMID:24004659]

10. Griswold DE, Webb EF, Badger AM, Gorycki PD, Levandoski PA, Barnette MA, Grous M, Christensen S, Torphy TJ. (1998) SB 207499 (Ariflo), a second generation phosphodiesterase 4 inhibitor, reduces tumor necrosis factor alpha and interleukin-4 production in vivo. J Pharmacol Exp Ther, 287 (2): 705-11. [PMID:9808700]

11. Habal FM, Huang VW. (2012) Review article: a decision-making algorithm for the management of pregnancy in the inflammatory bowel disease patient. Aliment Pharmacol Ther, 35 (5): 501-15. [PMID:22221203]

12. Hansel TT, Neighbour H, Erin EM, Tan AJ, Tennant RC, Maus JG, Barnes PJ. (2005) Glycopyrrolate causes prolonged bronchoprotection and bronchodilatation in patients with asthma. Chest, 128 (4): 1974-9. [PMID:16236844]

13. Huang Z, Dias R, Jones T, Liu S, Styhler A, Claveau D, Otu F, Ng K, Laliberte F, Zhang L et al.. (2007) L-454,560, a potent and selective PDE4 inhibitor with in vivo efficacy in animal models of asthma and cognition. Biochem Pharmacol, 73 (12): 1971-81. [PMID:17428447]

14. Huang Z, Mancini JA. (2006) Phosphodiesterase 4 inhibitors for the treatment of asthma and COPD. Curr Med Chem, 13 (27): 3253-62. [PMID:17168849]

15. Jones P, Storer RI, Sabnis YA, Wakenhut FM, Whitlock GA, England KS, Mukaiyama T, Dehnhardt CM, Coe JW, Kortum SW et al.. (2017) Design and Synthesis of a Pan-Janus Kinase Inhibitor Clinical Candidate (PF-06263276) Suitable for Inhaled and Topical Delivery for the Treatment of Inflammatory Diseases of the Lungs and Skin. J Med Chem, 60 (2): 767-786. [PMID:27983835]

16. Kalliomäki J, Attal N, Jonzon B, Bach FW, Huizar K, Ratcliffe S, Eriksson B, Janecki M, Danilov A, Bouhassira D et al.. (2013) A randomized, double-blind, placebo-controlled trial of a chemokine receptor 2 (CCR2) antagonist in posttraumatic neuralgia. Pain, 154 (5): 761-7. [PMID:23523116]

17. Kogan TP, Dupré B, Bui H, McAbee KL, Kassir JM, Scott IL, Hu X, Vanderslice P, Beck PJ, Dixon RA. (1998) Novel synthetic inhibitors of selectin-mediated cell adhesion: synthesis of 1,6-bis[3-(3-carboxymethylphenyl)-4-(2-alpha-D- mannopyranosyloxy)phenyl]hexane (TBC1269). J Med Chem, 41 (7): 1099-111. [PMID:9544210]

18. Lainé DI, McCleland B, Thomas S, Neipp C, Underwood B, Dufour J, Widdowson KL, Palovich MR, Blaney FE, Foley JJ et al.. (2009) Discovery of novel 1-azoniabicyclo[2.2.2]octane muscarinic acetylcholine receptor antagonists. J Med Chem, 52 (8): 2493-505. [PMID:19317446]

19. Lazaar AL, Miller BE, Tabberer M, Yonchuk J, Leidy N, Ambery C, Bloomer J, Watz H, Tal-Singer R. (2018) Effect of the CXCR2 antagonist danirixin on symptoms and health status in COPD. Eur Respir J, 52 (4). [PMID:30139779]

20. Lebwohl MG, Papp KA, Stein Gold L, Gooderham MJ, Kircik LH, Draelos ZD, Kempers SE, Zirwas M, Smith K, Osborne DW et al.. (2020) Trial of Roflumilast Cream for Chronic Plaque Psoriasis. N Engl J Med, 383 (3): 229-239. [PMID:32668113]

21. Lichtenstein GR, Hanauer SB, Sandborn WJ, Practice Parameters Committee of American College of Gastroenterology. (2009) Management of Crohn's disease in adults. Am J Gastroenterol, 104 (2): 465-83; quiz 464, 484. [PMID:19174807]

22. Lu S, Liu N, Dass SB, Reiss TF, Knorr BA. (2009) Randomized, placebo-controlled study of a selective PDE4 inhibitor in the treatment of asthma. Respir Med, 103 (3): 342-7. [PMID:19135348]

23. MacNee W, Allan RJ, Jones I, De Salvo MC, Tan LF. (2013) Efficacy and safety of the oral p38 inhibitor PH-797804 in chronic obstructive pulmonary disease: a randomised clinical trial. Thorax, 68 (8): 738-45. [PMID:23539534]

24. Millan DS, Bunnage ME, Burrows JL, Butcher KJ, Dodd PG, Evans TJ, Fairman DA, Hughes SJ, Kilty IC, Lemaitre A et al.. (2011) Design and synthesis of inhaled p38 inhibitors for the treatment of chronic obstructive pulmonary disease. J Med Chem, 54 (22): 7797-814. [PMID:21888439]

25. Miller BE, Mistry S, Smart K, Connolly P, Carpenter DC, Cooray H, Bloomer JC, Tal-Singer R, Lazaar AL. (2015) The pharmacokinetics and pharmacodynamics of danirixin (GSK1325756) - a selective CXCR2 antagonist - in healthy adult subjects. BMC Pharmacol Toxicol, 16 (1): 18. [PMID:26092545]

26. Moss RB, Mistry SJ, Konstan MW, Pilewski JM, Kerem E, Tal-Singer R, Lazaar AL, CF2110399 Investigators. (2013) Safety and early treatment effects of the CXCR2 antagonist SB-656933 in patients with cystic fibrosis. J Cyst Fibros, 12 (3): 241-8. [PMID:22995323]

27. Nickel JC, Egerdie B, Davis E, Evans R, Mackenzie L, Shrewsbury SB. (2016) A Phase II Study of the Efficacy and Safety of the Novel Oral SHIP1 Activator AQX-1125 in Subjects with Moderate to Severe Interstitial Cystitis/Bladder Pain Syndrome. J Urol, 196 (3): 747-54. [PMID:26968644]

28. O'Donoghue ML, Glaser R, Aylward PE, Cavender MA, Crisp A, Fox KA, Laws I, Lopez-Sendon JL, Steg PG, Theroux P et al.. (2015) Rationale and design of the LosmApimod To Inhibit p38 MAP kinase as a TherapeUtic target and moDify outcomes after an acute coronary syndromE trial. Am Heart J, 169 (5): 622-630.e6. [PMID:25965709]

29. Oliva J, Galasinski S, Richey A, Campbell AE, Meyers MJ, Modi N, Zhong JW, Tawil R, Tapscott SJ, Sverdrup FM. (2019) Clinically Advanced p38 Inhibitors Suppress DUX4 Expression in Cellular and Animal Models of Facioscapulohumeral Muscular Dystrophy. J Pharmacol Exp Ther, 370 (2): 219-230. [PMID:31189728]

30. Robichaud A, Stamatiou PB, Jin SL, Lachance N, MacDonald D, Laliberté F, Liu S, Huang Z, Conti M, Chan CC. (2002) Deletion of phosphodiesterase 4D in mice shortens alpha(2)-adrenoceptor-mediated anesthesia, a behavioral correlate of emesis. J Clin Invest, 110 (7): 1045-52. [PMID:12370283]

31. Rojas LA, Valentine E, Accorsi A, Maglio J, Shen N, Robertson A, Kazmirski S, Rahl P, Tawil R, Cadavid D et al.. (2020) p38α Regulates Expression of DUX4 in a Model of Facioscapulohumeral Muscular Dystrophy. J Pharmacol Exp Ther, 374 (3): 489-498. [PMID:32576599]

32. Stenton GR, Mackenzie LF, Tam P, Cross JL, Harwig C, Raymond J, Toews J, Wu J, Ogden N, MacRury T et al.. (2013) Characterization of AQX-1125, a small-molecule SHIP1 activator: Part 1. Effects on inflammatory cell activation and chemotaxis in vitro and pharmacokinetic characterization in vivo. Br J Pharmacol, 168 (6): 1506-18. [PMID:23121445]

33. Stevens T, Ekholm K, Gränse M, Lindahl M, Kozma V, Jungar C, Ottosson T, Falk-Håkansson H, Churg A, Wright JL et al.. (2011) AZD9668: pharmacological characterization of a novel oral inhibitor of neutrophil elastase. J Pharmacol Exp Ther, 339 (1): 313-20. [PMID:21791628]

34. Stocks MJ, Alcaraz L, Bailey A, Bowers K, Donald D, Edwards H, Hunt F, Kindon N, Pairaudeau G, Theaker J et al.. (2010) The discovery of new spirocyclic muscarinic M3 antagonists. Bioorg Med Chem Lett, 20 (24): 7458-61. [PMID:21036043]

35. Tzelepis G, Komanapolli S, Tyler D, Vega D, Fulambarker A. (1996) Comparison of nebulized glycopyrrolate and metaproterenol in chronic obstructive pulmonary disease. Eur Respir J, 9 (1): 100-3. [PMID:8834341]

36. Watz H, Bock D, Meyer M, Schierhorn K, Vollhardt K, Woischwill C, Pedersen F, Kirsten A, Beeh KM, Meyer-Sabellek W et al.. (2013) Inhaled pan-selectin antagonist Bimosiamose attenuates airway inflammation in COPD. Pulm Pharmacol Ther, 26 (2): 265-70. [PMID:23257347]