Asthma

Disease ID:1184
Name:Asthma
Associated with:6 targets
6 immuno-relevant targets
77 immuno-relevant ligands
Description
A bronchial disease characterized by chronic inflammation and narrowing of the airways; caused by a combination of environmental and genetic factors.
Database Links
Disease Ontology: DOID:2841
OMIM: 600807

Targets

ACKR1
Comments:  ACKR1 may play a role in the temporal regulation of asthma pathophysiology and symptoms.
MMP2
Comments:  MMP2 and MMP9 can promote the egress of inflammatory cells into airway lumen, suggesting a protective anti-inflammatory role in asthma. MMP2/MMP9 gelatinolytic activity is elevated in the sputum of asthmatic patients
MMP8
Comments:  MMP8 plays a protective role in asthma by promoting the clearance of recruited neutrophils.
MMP9
Comments:  MMP2 and MMP9 can promote the egress of inflammatory cells into airway lumen, suggesting a protective anti-inflammatory role in asthma. MMP2/MMP9 gelatinolytic activity is elevated in the sputum of asthmatic patients.
MMP12
Comments:  a common serine variant of the MMP12 gene in human (rs652438) causes more aggressive extracellular matrix degradation and is positively associated with disease severity. Thus MMP12 is a drug target for novel asthma therapeutics.
ADAM33
Comments:  ADAM33 is implicated in the pathology of asthma.

Ligands

Key to terms and symbols Click ligand name to view ligand summary Click column headers to sort
Ligand References Clinical and Disease comments
tamatinib
Immuno Disease Comments: This is the active metaboloite of fostamatinib and may have clinical utility in asthma.
Clinical Use: Tamatinib is a potential drug for treatment of the inflammation associated with and causing bronchial asthma resulting from allergen-induced airway hyperresponsiveness (AHR). The compound may have beneficial effects in additional inflammatory conditions, such as rheumatoid arthritis and other autoimmune conditions. | View clinical data
Bioactivity Comments: Autophosphorylation of FLT3 is inhibited by tamatinib [10]. Inhibition of RET by tamatinib is thought to be responsible for renal and ureteric agenesis observed in developmental toxicity tests carried out in rats and rabbits [15]. | View biological activity
risankizumab
Immuno Disease Comments: Phase 2 clinical candidate for asthma (see NCT02443298).
Clinical Use: Risankizumab has reached Phase II clinical trial for Crohn's disease (CD), psoriasis, and ankylosing spondylitis (AS). Results from the first-in-human proof-of-concept trial in patients with psoriasis are reported in [36]. | View clinical data
brodalumab
Immuno Disease Comments: Clinical candidate for asthma.
Clinical Use: Brodalumab was first approved in Japan (2016), and by the US FDA for plaque psoriasis the following year. Regulatory decisions are pending elsewhere. Clinical trials for the treatment of psoriatic arthritis (Phase III), moderate to severe plaque psoriasis (Phase III) and asthma (Phase II) are ongoing. Encouraging results from a Phase II study have been reported [45]. | View clinical data
Bioactivity Comments: BLAST searches using the peptide sequences of the heavy and light chains of brodalumab link to patent US7767206 [68], and monoclonal antibody clone AMH14/AML14. | View biological activity
tiotropium
Immuno Disease Comments: Bronchodilator used as maintenance therapy for asthma.
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
theophylline
Immuno Disease Comments: Approved drug for asthma.
Clinical Use: Used in the treatment of symptoms and reversible airways obstruction in conditions such as asthma, emphysema and chronic bronchitis. | View clinical data
salbutamol
Immuno Disease Comments: Used to treat bronchospasm due to asthma.
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
salmeterol
Immuno Disease Comments: Used to treat bronchospasm due to asthma.
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
IL-33
Immuno Disease Comments: An IL-1 family cytokine involved in the initiation of the type 2 immune response during parasitic infection and allergic diseases such as asthma. IL-33 is an investigational therapeutic target for asthma.
venetoclax 67
Immuno Disease Comments: Venetoclax (ABT-199) has been shown to induce apoptosis of airway inflammatory cells (eosinophils, neutrophils, Th2, Th17 and dendritic cells) suggesting a potiential role in management of eosinophilic or corticosteroid resistant-neutrophilic airway inflammation.
Clinical Use: Venetoclax (in combination with and in comparison with currently approved anti-neoplastics) was assessed in Phase III clinical trials as a potential treatment for chronic lymphocytic leukemia (CLL). See NCT02005471 and NCT02242942 for full details.
In January 2016, the US FDA granted venetoclax (in combination with hypomethylating agents) breakthrough designation as a first-line treatment for patients with acute myeloid leukemia (AML) who are ineligible to receive high-dose chemotherapy.

Full marketing authorisation: In April 2016, the US FDA granted full approval for venetoclax as an oral treatment regimen for patients with chronic lymphocytic leukemia (CLL) with 17p deletion (or TP53 mutation) (detected by an FDA-approved test), who have received at least one prior therapy. EMA approval followed in December 2016. In June 2018, the FDA expanded approval to include treatment of both CLL and small lymphocytic lymphoma (SLL), with or without 17p deletion in patients who have received at least one prior therapy. This approval is for a combined regimen using venetoclax plus the anti-CD20 monoclonal [60], and offers a chemotherapy-free option for CLL patients. | View clinical data
Bioactivity Comments: Venetoclax is reported to be >4800-fold more selective for Bcl-2 compared to other protein family members Bcl-xL and Bcl-w [62]. | View biological activity
GSK2245035
Immuno Disease Comments: Experimental compound with clinical potential in asthma.
Clinical Use: GSK2245035 has completed Phase 2 clinical trials in patients with asthma and allergic rhinitis. Results from early clinical evaluation in trials for allergic rhinitis, NCT01480271 (Phase 1) and NCT01607372 (Phase 2), are reported in [69], and results from NCT02446613 reported in [20]. | View clinical data
Bioactivity Comments: In vivo findings disclosed in WO2010018133 report that GSK2245035 (Example 22) induces IFNα production, with mean serum levels reaching 21029 pg/ml (none detected in control mice) [8]. Early clinical trial results show clear target engagement at a dose of 20ng (as detected by local and peripheral increase of IFN-gamma-inducible protein-10) and an accceptable safety profile doses acheiving a local TLR7-mediated immune response [69]. Doses above 100ng were associated with undesireable cytokine release syndrome-related symptoms.

Direct binding assays have not been performed for this compound, rather its engagement with TLR7 has been assessed in functional assays measuring ligand-induced increases in downstream cytokine production/release [7]. An EC50 of ~4.5nM for IFNα production in PBMCs is reported [7]. | View biological activity
GW766994
Immuno Disease Comments: Phase 2 clinical candidate for mild-moderate asthma (NCT01160224).
Clinical Use: GW766994 has completed Phase 2 clinical trial (NCT01160224) in patients with mild-moderate asthma who have high sputum eosinophilia. Safety and efficacy in early clinical trial are reported by Neighbour et al. (2014) [49]. | View clinical data
compound 7f [PMID: 29283260] 44
Immuno Disease Comments: 7f has shown efficacious anti-inflammatory activity in HDM-induced allergic airway inflammation in mice.
Bioactivity Comments: 7f is selective for human and mouse AMCase (CHIA) over the related chitinase CHIT1 (~16-fold for human and >150-fold for mouse enzymes) [44]. | View biological activity
MK-0359
Immuno Disease Comments: Completed Phase 2 clinical evaluation in asthma- see NCT00482898
Clinical Use: MK-0359 exhibited clinical efficacy in a Phase 2 study in asthma patients (NCT00482898), but caused gastrointestinal adverse effects [40]. 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 [32]. 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 [56], 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 [40]. | View biological activity
UCB4144
Immuno Disease Comments: Phase 1 clinical candidate for asthma- see NCT02473939
Clinical Use: UCB4144 (as research code VR942) has completed Phase 1 clinical trial in healthy subjects and patients with mild asthma. Positive results are reported in an abstract presented at the American Thoracic Society International Conference in Washington DC in 2017 (Abstract 4681), but these results have not been formally published in a peer-reviewed article. | View clinical data
levosalbutamol
Immuno Disease Comments: Approved inhalation drug for treating/preventing asthma attacks.
Clinical Use: Levosalbutamol is a SABA drug administered by inhalation, for the prevention or treatment of airway obstruction in asthmatic patients (≥4 years-adults). | View clinical data
Bioactivity Comments: Note that clinically administered formulations can contain the tartrate, sulphate or hydrochloride salts of levosalbutamol. | View biological activity
ipratropium
Immuno Disease Comments: Bronchodilator used in treatment for bronchospasm in asthma.
Clinical Use: Used to treat bronchospasm associated with chronic obstructive pulmonary disease (COPD). | View clinical data
cetirizine
Immuno Disease Comments: Non-sedating antihistamine approved for allergic rhinitis, chronic urticaria, and pollen-induced asthma.
Clinical Use: Cetirizine is used to control the symptoms of allergic rhinitis, chronic urticaria, and pollen-induced asthma. It does not cause the drowsiness associated with some other antihistamines. In many countries this drug is available without a prescription. An ophthalmic solution containing cetirizine hydrochloride (0.24%, Zerviate®) was FDA approved in June 2017. | View clinical data
Bioactivity Comments: In rodent studies, systemically administered cetirizine shows negligible brain penetration or binding to cerebral H1 receptors. | View biological activity
dexamethasone
Immuno Disease Comments: Glucocorticoid drug used to treat many inflammatory condtions including asthma.
Clinical Use: Dexamethasone may be administered by various routes to treat myriad inflammatory condtions, including inflammatory dermatoses, asthma, allergic or inflammatory nasal conditions, and nasal polyps, endocrine disorders and many more. | View clinical data
prednisolone
Immuno Disease Comments: Glucocorticoid drug used to treat many inflammatory condtions including asthma.
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
zafirlukast
Immuno Disease Comments: Leukotriene receptor antagonist approved for the treatment of asthma.
Clinical Use: Used in the prophylaxis and chronic treatment of asthma. | View clinical data
Bioactivity Comments: Zafirlukast shows low potency off-target effects on PPARγ and soluble epoxide hydrolase (sEH) [59]. | View biological activity
montelukast
Immuno Disease Comments: Leukotriene receptor antagonist approved for the treatment of asthma.
Clinical Use: Used in the treatment of asthma. | View clinical data
procaterol
Immuno Disease Comments: β2-adrenoceptor agonist approved outside of the EU and US for the treatment of asthma.
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 asthma.
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
zileuton
Immuno Disease Comments: 5-LOX inhibitor approved to treat asthma.
Clinical Use: Used in the prophylaxis and chronic treatment of asthma. | View clinical data
beclometasone dipropionate
Immuno Disease Comments: Glucocorticoid drug used to treat asthma.
Clinical Use: Used in the management of asthma symptoms and the treatment of allergic rhinitis. | View clinical data
Bioactivity Comments: As this drug is a prodrug it is unlikely to have signifivcant affinity for the glucocorticoid receptor. Therefore we have not tagged a primary target for this drug. | View biological activity
tranilast
Immuno Disease Comments: An approved drug with some antihistaminergic action..
Clinical Use: Approved to treat bronchial asthma and keloid and hypertrophic scars. There is no information regarding approval for clinical use of this drug on the US FDA or European Medicines Agency websites. Individual national approval agencies may have granted marketing authorisation. | View clinical data
JNJ-10311795
Immuno Disease Comments: An experimental dual inhibitor of the leukocyte proteases cathepsin G and chymase with potential anti-inflammatory activity.
fluticasone
Immuno Disease Comments: Glucocorticoid (corticosteroid) drug used to treat asthma.
Clinical Use: The approved drug can contain fluticasone propionate. This formulation is used to treat various inflammatory conditions including aleviation of inflammatory and pruritic symptoms of dermatoses and psoriasis (applied topically), for controlling symptoms of allergic and non-allergic rhinitis (used intranasally) and to treat asthma (inhalation and oral administration). Fluticasone furoate (in Flonase® SensimistTM Allergy Relief) is approved as an over-the-counter medication providing non-drowsy, 24-hour relief of both nose- and eye-related allergy symptoms. | View clinical data
beclometasone
Immuno Disease Comments: A glucocorticoid (corticosteroid) drug used to treat asthma.
Clinical Use: Used for the prophylaxis of asthma. 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. | View clinical data
omalizumab
Immuno Disease Comments: An anti-IgE therapy approved to treat persistent and severe asthma inadequately controlled by inhaled corticosteroids.
Clinical Use: Used to treat moderate to severe IgE-mediated (i.e. allergy triggered) persistent asthma (US) or severe asthma (EU) [11], in adults and children over 12 years old, inadequately controlled by inhaled corticosteroid treatment. In 2014 the US FDA approved use of this drug for the treatment of chronic idiopathic urticaria (CIU, a.k.a. chronic spontaneous urticaria) which is unresponsive to treatment with anti-histamine H1 receptor drugs.
In July 2016, the FDA expanded asthma approval to include children six to 11 years of age, as indicated previously for those 12 years-adult. | View clinical data
roflumilast
Immuno Disease Comments: A phosphodiesterase inhibitor approved to treat asthma.
Clinical Use: Roflumilast is used to treat asthma and chronic obstructive pulmonary disease (COPD) [33]. 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 asthma.
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
flunisolide
Immuno Disease Comments: A glucocorticoid (corticosteroid) drug used to treat asthma.
Clinical Use: Flunisolide use is indicated to prevent asthma attacks and to treat allergic rhinitis. | View clinical data
fluticasone propionate
Immuno Disease Comments: For long-term prevention of bronchospasm in asthmatic patients.
Clinical Use: Fluticasone propionate is used for long-term prevention of bronchospasm in asthmatic patients and also is also contained in creams and nasal sprays to control allergy symptoms. In the US, fluticasone propionate is available over-the-counter, as Flonase Allergy Relief®. | View clinical data
isoetarine
Immuno Disease Comments: A bronchodilator used to manage asthma.
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
tripelennamine
Immuno Disease Comments: Antihistamine approved for allergic asthma.
Clinical Use: Used as an antipruritic and antihistamine in the treatment of asthma, hay fever, rhinitus and urticaria. All formulations of this drug appear to have been discontinued by the US FDA, although other national approval agencies may continue to grant marketing authorisation. | View clinical data
vilanterol
Immuno Disease Comments: Used in combination with fluticasone furoate to manage asthma symptoms.
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
budesonide
Immuno Disease Comments: A glucocorticoid (corticosteroid) drug used to treat asthma.
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) [39], inflammatory skin disorders, allergic rhinitis and in an extended release formulation, ulcerative colitis [27]. 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 asthma.
Clinical Use: Indacaterol is a very long-acting, rapid onset β2-adrenoceptor agonist [13] 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
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) [70] and asthma [29]. 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) [63]. | View biological activity
ciclesonide
Immuno Disease Comments: A glucocorticoid (corticosteroid) drug used to treat asthma.
Clinical Use: Ciclesonide is an inhalation glucocorticoid. It is approved to treat inflammatory/obstructive airway diseases such as persistent asthma. | View clinical data
Bioactivity Comments: The IC50 for ciclesonide at the human glucocorticoid receptor is 210nM, compared to 1.75nM for the active metabolite, desisobutyrylciclesonide. Ki values show the same pattern of higher affinity of desisobutyrylciclesonide (37nM for ciclesonide vs 0.31nM for desisobutyrylciclesonide) [6]. | View biological activity
arformoterol
Immuno Disease Comments: A LABA used to treat asthma.
Clinical Use: Arformoterol is indicated for the treatment of chronic obstructive pulmonary disease (COPD) and asthma. | View clinical data
olodaterol
Immuno Disease Comments: A LABA used to treat asthma.
Clinical Use: Olodaterol was approved by the FDA in July 2014 as an inhalation medication for the treatment of chronic obstructive pulmonary disease (COPD). Phase II trials have also been conducted in patients with asthma (see NCT01013753).
This drug has been further assessed in clinical trials in combination with the muscarinic antagonist bromide (also a bronchodilator).
In May 2015 the US FDA approved a fixed-dose combination of bromide and olodaterol (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.
Click here to view a full list of associated trials registered with ClinicalTrials.gov. | View clinical data
dupilumab
Immuno Disease Comments: Clinical candidate for asthma (see NCT02134028, Phase 3).
Clinical Use: Dupilumab is being clinically assessed as a treatment for atopic allergic conditions, including asthma, atopic dermatitis (AD) and nasal polyposis. A list of trials registered at ClinicalTrials.gov is available here.
Preliminary results from one clinical trial in patients with persistent asthma, reports significant improvements in measures of lung function and asthma control when treated with dupilumab [72].
Results from a Phase II study in patients with nasal polyposis and chronic symptoms of sinusitis (NCT01920893) are reported by Bachert et al. (2016) [3]. Patients in this study were given dupilumab + or mometasone + dupilumab placebo. Dupilumab + mometasone reduced nasal polyp burden and improved symptoms of sinusitis to a greater extent than the mometasone + placebo treatment.
Dupilumab received full FDA approval for moderate-to-severe eczema (atopic dermatitis) in March 2017, and the EMA granted this same approval in August 2017. | View clinical data
Bioactivity Comments: Affinity data in the table below is taken from patent US7608693 [41], using antibody clone H4H098P as a representative example of the embodiment of the patent. The clone becoming dupilumab is not reported. | View biological activity
nedocromil
Immuno Disease Comments: Inhalation mast cell stabiliser used to treat asthma.
Clinical Use: Used as an inhlation drug to alleviate bronchconstriction in asthma [37], and may be used in eye-drops to treat allergic eye reactions. The use of some formulations of this drug has been discontinued in the US. | View clinical data
Bioactivity Comments: As the precise MMOA of this drug has not been fully resolved, we have not tagged a primary drug target in this case. | View biological activity
cromoglicic acid
Immuno Disease Comments: Mast cell stabiliser used to treat asthma.
Clinical Use: Cromoglicic acid is available in different formulations; nasal spray is used to treat allergic rhinitis, nebulizer solution to treat asthma, eye drops to treat allergic conjunctivitis and an oral form to treat mastocytosis,dermatographic urticaria and ulcerative colitis.
Recent reports suggest that cromolyn inhibits glycogen synthase kinase 3β and may therefore have potential to treat diabetes and obesity [46] and may prove effective in treating insulin-induced lipoatrophy [55]. | View clinical data
Bioactivity Comments: As the precise MMOA of this drug has not been fully resolved, we have not tagged a primary drug target in this case. | View biological activity
AZD1981
Immuno Disease Comments: Phase 2 clinical candidate with predicted anti-asthmatic activity (see NCT00758589 for example). Has alos completed Phase 2 clinical trials for COPD (NCT00690482) and chronic idiopathic urticaria (NCT02031679).
Bioactivity Comments: Data for 48 analogues from the reference given are listed in PubChem BioAssay 630011 | View biological activity
lebrikizumab
Immuno Disease Comments: Repurposed clinical candidate for asthma (Phase 3).
Clinical Use: This antibody was originally tested as a treatment for refractory Hodgkin's lymphoma but was later repurposed as a potential asthma treatment [16]. The antibody entered Phase 2 trial for idiopathic pulmonary fibrosis (IPF) and Phase 3 trial for asthma. Business reports online indicate that Roche have discontinued lebrikizumab development in IPF following mixed results from their trials [1]. Click here to view ClinicalTrails.gov's listing of current lebrikizumab trials. | View clinical data
Bioactivity Comments: In humans lebrikizumab has systemic effects on markers of Th2 inflammation. Lebrikizumab treatment reduces serum immunoglobulin E (IgE) and interleukin-13 and -17 levels by approximately 25% [58].
The development of lebrikizumab is covered by patent US7674459, in which it appears to be the monoclonal designated as 228B/C-1 [24]. No binding constant is provided in this patent, although a graph representing binding of 228B/C-1 to IL-13 in an ELISA suggests a half max value of approximately 0.1nM. | View biological activity
mepolizumab
Immuno Disease Comments: Approved therapeutic for severe asthma exacerbations.
Clinical Use: In November 2015, the US FDA approved mepolizumab for the treatment of severe asthma exacerbations in patients who are already taking other asthma medications [5,51].
In the United States and the European Union, mepolizumab can be used under orphan drug designation for the treatment of Churg-Strauss syndrome and hypereosinophilic syndrome.
To gain full marketing authorisation, mepolizumab is being evaluated in clinical trials in patients with eosinophilic COPD (Phase III), hypereosinophilic syndrome (HES; Phase III) and for eosinophilic granulomatosis with polyangiitis (EGPA or Churg-Strauss Syndrome; Phase III). Click here to view ClinicalTrials.gov's listing of current mepolizumab trials. | View clinical data
Bioactivity Comments: Smith et al (2011) cite an IC50 of 0.94nM for mepolizumab-induced inhibition of IL-5 binding to its receptor [61], although the citation for this data is a GlaxoSmithKline investigators’ brochure for mepolizumab, so is not peer reviewed or easily accessed. | View biological activity
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
pascolizumab
Immuno Disease Comments: Clinical candidate therapeutic for asthma (Phase 2 study NCT00024544 completed), but not progressed since 2012.
Clinical Use: Pascolizumab is in phase II clinical trial for asthma (see NCT00024544) and pulmonary tuberculosis (TB; see NCT01638520). | View clinical data
tralokinumab
Immuno Disease Comments: Phase 3 clinical candidate for uncontrolled asthma (see NCT02161757).
Clinical Use: Tralokinumab reached Phase 3 clinical trials for uncontrolled asthma, and atopic dermatitis, and Phase 2 for alopecia areata. Click here to link to ClinicalTrials.gov's listing of Phase III tralokinumab trials. In addition, Phase 2 trials are investigating tralokinumab as a treatment for idiopathic pulmonary fibrosis (IPF, NCT01629667 and NCT02036580). Business reports online indicate that AstraZeneca have discontinued tralokinumab development as it showed no benefit over placebo in their STRATOS 2 and TROPOS late-stage asthma trials [1]. | View clinical data
reslizumab
Immuno Disease Comments: Approved therapeutic as maintenance treatment for asthma in combination with other asthma medications.
Clinical Use: A Phase III clinical trial of reslizumab as a treatment for eosinophilic asthma (NCT01287039) has been completed, and results are published in [18].
In March 2016, the US FDA approved reslizumab for use with other asthma medicines for the maintenance treatment of severe asthma in adult patients. | View clinical data
benralizumab 19
Immuno Disease Comments: Approved drug for severe eosinophilic asthma.
Clinical Use: In November 2017, the US FDA approved benralizumab as an add-on maintenance treatment for patients with severe eosinophilic phenotype asthma (aged 12 years and older). EMA marketing approval is pending a final decision, with their Committee for Medicinal Products for Human Use (CHMP) having recommended marketing authorisation on 9th November 2017 [21]. Results from Phase 3 clinical trial NCT01914757 are published in [23]. Analysis of trial outcomes show that not all asthma patients will respond to benralizumab, but that in patients with high eosinophil counts (> 300 cells per μL) annual exacerbation rates were significantly reduced. These suggest that targeting the biologic to specific patient populations will provide most clinical benefit. Click here to view ClinicalTrials.gov's listing of current benralizumab trials. | View clinical data
amelubant
Immuno Disease Comments: No progress in development beyond Phase 2 trial in asthma.
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 [9]. Bioactivity is attributed to its active metabolite, . | View biological activity
example 131 [WO2009133348]
Immuno Disease Comments: A compound developed with predicted clinical utility in asthma.
Bioactivity Comments: Example 131 is inactive against other trypsin-like serine proteases (plasma kallikrein, thrombin, trypsin and plasmin) [22]. | View biological activity
navarixin
Immuno Disease Comments: Completed Phase 2 clinical trial NCT00632502 for asthma.
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
dectrekumab
Immuno Disease Comments: Phase 2 trial NCT01479595 in asthma has been completed.
Clinical Use: Dectrekumab (QBX258) reached Phase II clinical trial as a potential biologic therapy for several immune conditions, including idiopathic pulmonary fibrosis (IPF), asthma, eosinophilic esophagitis [57] (proof of principle study NCT01022970), Crohn's disease, keloids and allergic rhinitis. As of May 2017, there are no active dectrekumab studies. | View clinical data
tezepelumab
Immuno Disease Comments: Clinical candidate for asthma (Phase 2).
Clinical Use: Tezepelumab is being evaluated in clinical trials as a potential immunomodulatory agent for uncontrolled (especially noneosinophilic type) asthma (Phase 2- results of NCT02054130 published in [17]) and atopic dermatitis (AD; Phase 1). Click here to link to ClinicalTrials.gov's full listing of tezepelumab (research coded AMG 157 or MEDI9929) trials. | View clinical data
enokizumab
Immuno Disease Comments: Clinical candidate for asthma (maximum Phase 2).
Clinical Use: Enokizumab has been evaluated in Phase II clinical trials as a potential anti-asthmatic therapy [50,53]. Click here to link to ClinicalTrials.gov's full listing of Phase II enokizumab (research coded MEDI528 or MEDI0528) trials. | View clinical data
lenzilumab
Immuno Disease Comments: Clinical candidate for asthma (maximum Phase 2).
Clinical Use: Lenzilumab has completed Phase II clinical trial for uncontrolled asthma, whereas a Phase II study in patients with inadequately controlled rheumatoid arthritis has been terminated. A Phase I trial in patients with previously treated chronic myelomonocytic leukemia (CMML) is ongoing [52]. | View clinical data
JNJ-39758979
Immuno Disease Comments: See completed clinical trial NCT00946569
Clinical Use: Phase 2a clinical trial results in patients with moderate atopic dermatitis are published in [48] which indicate that the study did not meet its primary end-point, and produced drug-induced agranulocytosis, explaining its termination. Phase 2 trial NCT00946569 in asthma patients has been completed. | View clinical data
Bioactivity Comments: Preclinical data are reported in [65]. | View biological activity
fevipiprant
Immuno Disease Comments: Phase 3 clinical candidate for Asthma.
Clinical Use: Phase III clinical trials evaluating QAW039 in asthma patients (NCT02555683 and NCT02563067) are registered with ClinicalTrials.gov.

Phase II trial results are published in [25] and report that fevipiprant is well tolerated and reduces eosinophilic airway inflammation in patients with persistent moderate-to-severe asthma resistant to inhaled corticosteroid treatment (i.e. patients maintaining raised sputum eosinophil counts whilst using corticosteroids). | View clinical data
Bioactivity Comments: Fevipiprant has a slower dissociation rate than its parent structure [64]. | View biological activity
QAV680
Immuno Disease Comments: Completed Phase 2 trial in asthma (see NCT00814216).
Clinical Use: QAV680 reached Phase II clinical trial in asthma and allergic rhinitis. As of May 2017, there are no active clinical trials evaluating this compound. | View clinical data
ligelizumab
Immuno Disease Comments: No progress in development beyond Phase 2.
Clinical Use: Several Phase II clinical trials are underway to evaluate the potential of QGE031 as a treatment for asthma and chronic spontaneous urticaria [43]. | View clinical data
mometasone
Immuno Disease Comments: A corticosteroid drug used in the management of asthma, and topically for allergic skin disorders.
Clinical Use: Mometasone is used intranasally in the management of asthma, allergic rhinitis and nasal polyposis, and topically for allergic skin disorders. Prescribed formulations contain mometasone furoate (PubChem CID 441336). | View clinical data
PF-04191834
Immuno Disease Comments: No progress beyond Phase 2 trial.
Clinical Use: A Phase II clinical trial evaluating the brochodilatory effect of a single dose of PF-04191834 in patients with asthma has been completed. A Phase II study in osteoarthritis was terminated. | View clinical data
Bioactivity Comments: PF-4191834 is 300-fold selective for 5-LOX compared to 12-LOX (ALOX12) and 15-LOX (ALOX15) and does not inhibit the cyclooxygenase (COX) enzymes [42]. | View biological activity
GSK583
Immuno Disease Comments: Experimental compound with predicted application in asthma.
Bioactivity Comments: A kinome scan shows that at 1µM GSK583 is selective for RIP2 kinase in the panel of 300 kinases tested [28]. GSK583 is effective in cellular asays assessing its ability to inhibit pro-inflammatory cytokine release in response to NOD2 pathway actvation by muramyldipeptide (MDP). | View biological activity
toreforant
Immuno Disease Comments: No progress beyond Phase 2 trial.
Clinical Use: Toreforant failed to show clinical efficacy in a Phase 2 clinical trial in patients with active rheumatoid arthritis [66]. Phase 2 studies NCT01823016 and NCT02295865 in patients with uncontrolled, persistent asthma and moderate to severe plaque-type psoriasis respectively have been completed. | View clinical data
timapiprant
Immuno Disease Comments: Phase 2 clinical candidate for asthma, including refractory eosinophilic asthma.
Clinical Use: OC000459 is being evaluated in several Phase 2 clinical trials in various inflammatory and allergic conditions including asthma, allergic rhinitis and atopic dermatitis. Click here to link to a list of Phase 2 OC000459 trials registered with ClinicalTrials.gov. | View clinical data
Bioactivity Comments: OC000459 inhibits mast cell-dependent activation of human Th2 lymphocytes and eosinophils [54]. It does not antagonise ligand binding at any of the other prostanoid receptors [54]. | View biological activity
AZD7594
Immuno Disease Comments: No progress beyond Phase 2 trial.
Clinical Use: AZD7594 has completed Phase 2 clinical trial in patients with mild to moderate asthma, in which it demonstrated dose-dependent efficacy (see NCT02479412). | View clinical data
Bioactivity Comments: AZD7594 transrepresses transctiption of GR-induced genes with an IC50 of 55nM [31]. | View biological activity
abediterol
Immuno Disease Comments: No progress beyond Phase 2 trial.
Clinical Use: Phase 2a first-in-patient clinical trial results are published in [4]. 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
CDP840
Immuno Disease Comments: An experimental selective PDE4 inhibitor, developed for anti-inflammatory activity.
Bioactivity Comments: In human asthmatic subjects oral CDP840 attenuated the late asthmatic response to allergen by 30% compared to placebo [30]. The treatment was well tolerated and showed no bronchodilatory or histamine antagonist effect. | View biological activity
nemiralisib
Immuno Disease Comments: Completed Phase 1 trial in asthma (see NCT01462617).
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
example 36 [WO2016177845] 35
Immuno Disease Comments: A novel LTC4S inhibitor with potential anti-inflammatory effects in respiratory conditions such as asthma.
IgE heavy chain
Immuno Disease Comments: Target of approved anti-asthmatic biological omalizumab.
ABT-737 67
Immuno Disease Comments: ABT-737 has been shown to induce apoptosis of airway inflammatory cells (eosinophils, neutrophils, Th2, Th17 and dendritic cells) suggesting a potiential role in management of eosinophilic or corticosteroid resistant-neutrophilic airway inflammation.
Clinical Use: ABT-737 has been assessed in a Phase II clinical trial investigating its effects on ex vivo ovarian cancer samples from patients [34,38,73]. | View clinical data

References

Show »

1. Adams B. Sanofi ditches IL-4/IL-13 antibody drug in lung-scarring disease. Accessed on 09/02/2018. Modified on 09/02/2018. fiercebiotech.com, https://www.fiercebiotech.com/biotech/sanofi-ditches-il4-il13-antibody-drug-lung-scarring-disease

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. Bachert C, Mannent L, Naclerio RM, Mullol J, Ferguson BJ, Gevaert P, Hellings P, Jiao L, Wang L, Evans RR et al.. (2016) Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal Polyposis: A Randomized Clinical Trial. JAMA, 315 (5): 469-79. [PMID:26836729]

4. 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]

5. Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, Ortega HG, Pavord ID, SIRIUS Investigators. (2014) Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N. Engl. J. Med., 371 (13): 1189-97. [PMID:25199060]

6. Belvisi MG, Bundschuh DS, Stoeck M, Wicks S, Underwood S, Battram CH, Haddad el-B, Webber SE, Foster ML. (2005) Preclinical profile of ciclesonide, a novel corticosteroid for the treatment of asthma. J. Pharmacol. Exp. Ther., 314 (2): 568-74. [PMID:15878996]

7. Biggadike K, Ahmed M, Ball DI, Coe DM, Dalmas Wilk DA, Edwards CD, Gibbon BH, Hardy CJ, Hermitage SA, Hessey JO et al.. (2016) Discovery of 6-Amino-2-{[(1S)-1-methylbutyl]oxy}-9-[5-(1-piperidinyl)pentyl]-7,9-dihydro-8H-purin-8-one (GSK2245035), a Highly Potent and Selective Intranasal Toll-Like Receptor 7 Agonist for the Treatment of Asthma. J. Med. Chem., 59 (5): 1711-26. [PMID:26861551]

8. Biggadike K, Coe DM, Lewell XQ, Mitchell CJ, Smith SA, Trivedi N. (2010) Purine derivatives for use in the treatment of allergic, inflammatory and infectious diseases. Patent number: WO2010018133. Assignee: Smithkline Beecham Corporation. Priority date: 11/08/2008. Publication date: 18/02/2010.

9. 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]

10. Braselmann S, Taylor V, Zhao H, Wang S, Sylvain C, Baluom M, Qu K, Herlaar E, Lau A, Young C et al.. (2006) R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J. Pharmacol. Exp. Ther., 319 (3): 998-1008. [PMID:16946104]

11. Busse W, Corren J, Lanier BQ, McAlary M, Fowler-Taylor A, Cioppa GD, van As A, Gupta N. (2001) Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J. Allergy Clin. Immunol., 108 (2): 184-90. [PMID:11496232]

12. Cataldo D, Munaut C, Noël A, Frankenne F, Bartsch P, Foidart JM, Louis R. (2000) MMP-2- and MMP-9-linked gelatinolytic activity in the sputum from patients with asthma and chronic obstructive pulmonary disease. Int. Arch. Allergy Immunol., 123 (3): 259-67. [PMID:11112863]

13. 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]

14. Chapman DG, Mougey EB, Van der Velden JL, Lahue KG, Aliyeva M, Daphtary N, George KL, Hoffman SM, Schneider RW, Tracy RP et al.. (2017) The Duffy antigen receptor for chemokines regulates asthma pathophysiology. Clin. Exp. Allergy, 47 (9): 1214-1222. [PMID:28471517]

15. Clemens GR, Schroeder RE, Magness SH, Weaver EV, Lech JW, Taylor VC, Masuda ES, Baluom M, Grossbard EB. (2009) Developmental toxicity associated with receptor tyrosine kinase Ret inhibition in reproductive toxicity testing. Birth Defects Res. Part A Clin. Mol. Teratol., 85 (2): 130-6. [PMID:19107952]

16. Corren J, Lemanske RF, Hanania NA, Korenblat PE, Parsey MV, Arron JR, Harris JM, Scheerens H, Wu LC, Su Z et al.. (2011) Lebrikizumab treatment in adults with asthma. N. Engl. J. Med., 365 (12): 1088-98. [PMID:21812663]

17. Corren J, Parnes JR, Wang L, Mo M, Roseti SL, Griffiths JM, van der Merwe R. (2017) Tezepelumab in Adults with Uncontrolled Asthma. N. Engl. J. Med., 377 (10): 936-946. [PMID:28877011]

18. Corren J, Weinstein S, Janka L, Zangrilli J, Garin M. (2016) Phase 3 Study of Reslizumab in Patients With Poorly Controlled Asthma: Effects Across a Broad Range of Eosinophil Counts. Chest, 150 (4): 799-810. [PMID:27018175]

19. Drugs.com. FDA Approves Fasenra. Accessed on 16/11/2017. Modified on 16/11/2017. drugs.com, https://www.drugs.com/newdrugs/fda-approves-fasenra-benralizumab-severe-eosinophilic-asthma-4633.html?utm_source=ddc&utm_medium=email&utm_campaign=FDA+Approves+Fasenra+%28benralizumab%29+for+Severe+Eosinophilic+Asthma

20. Ellis AK, Tsitoura DC, Quint D, Powley W, Lee LA. (2017) Safety and pharmacodynamics of intranasal GSK2245035, a TLR7 agonist for allergic rhinitis: A randomized trial. Clin. Exp. Allergy, 47 (9): 1193-1203. [PMID:28681506]

21. European Medicines Agency. Fasenra. Accessed on 16/11/2017. Modified on 16/11/2017. ema.europa.eu, http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/004433/smops/Positive/human_smop_001219.jsp&mid=WC0b01ac058001d127&source=homeMedSearch&category=human

22. 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.

23. FitzGerald JM, Bleecker ER, Nair P, Korn S, Ohta K, Lommatzsch M, Ferguson GT, Busse WW, Barker P, Sproule S et al.. (2016) Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet, 388 (10056): 2128-2141. [PMID:27609406]

24. Fung SC, Moyle M. (2010) Treatment of Interleukin13 dependent neoplastic disorders. Patent number: US7674459. Assignee: Genentech, Inc.. Priority date: 23/12/2003. Publication date: 09/03/2010.

25. Gonem S, Berair R, Singapuri A, Hartley R, Laurencin MFM, Bacher G, Holzauer B, Bourne M, Mistry V, Pavord ID et al.. (2016) Fevipiprant, a prostaglandin D2 receptor 2 antagonist, in patients with persistent eosinophilic asthma: a single-centre, randomised, double-blind, parallel-group, placebo-controlled trial. The Lancet,.

26. Gueders MM, Balbin M, Rocks N, Foidart JM, Gosset P, Louis R, Shapiro S, Lopez-Otin C, Noël A, Cataldo DD. (2005) Matrix metalloproteinase-8 deficiency promotes granulocytic allergen-induced airway inflammation. J. Immunol., 175 (4): 2589-97. [PMID:16081833]

27. 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]

28. Haile PA, Votta BJ, Marquis RW, Bury MJ, Mehlmann JF, Singhaus Jr R, Charnley AK, Lakdawala AS, Convery MA, Lipshutz DB et al.. (2016) The Identification and Pharmacological Characterization of 6-(tert-Butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine (GSK583), a Highly Potent and Selective Inhibitor of RIP2 Kinase. J. Med. Chem., 59 (10): 4867-80. [PMID:27109867]

29. 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]

30. Harbinson PL, MacLeod D, Hawksworth R, O'Toole S, Sullivan PJ, Heath P, Kilfeather S, Page CP, Costello J, Holgate ST, Lee TH. (1997) The effect of a novel orally active selective PDE4 isoenzyme inhibitor (CDP840) on allergen-induced responses in asthmatic subjects. Eur Respir J., 10 (5): 1008-14. [PMID:9163639]

31. Hemmerling M, Nilsson S, Edman K, Eirefelt S, Russell W, Hendrickx R, Johnsson E, Kärrman Mårdh C, Berger M, Rehwinkel H et al.. (2017) Selective Nonsteroidal Glucocorticoid Receptor Modulators for the Inhaled Treatment of Pulmonary Diseases. J. Med. Chem., 60 (20): 8591-8605. [PMID:28937774]

32. 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]

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

34. Jain HV, Meyer-Hermann M. (2011) The molecular basis of synergism between carboplatin and ABT-737 therapy targeting ovarian carcinomas. Cancer Res., 71 (3): 705-15. [PMID:21169413]

35. Kleinschmidt TK, Haraldsson M, Basavarajappa D, Lundeberg E, Thulasingam M, Ekoff M, Fauland A, Lehmann C, Kahnt AS, Lindbom L et al.. (2015) Tandem Benzophenone Amino Pyridines, Potent and Selective Inhibitors of Human Leukotriene C4 Synthase. J. Pharmacol. Exp. Ther., 355 (1): 108-16. [PMID:26283693]

36. Krueger JG, Ferris LK, Menter A, Wagner F, White A, Visvanathan S, Lalovic B, Aslanyan S, Wang EE, Hall D et al.. (2015) Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial. J. Allergy Clin. Immunol., 136 (1): 116-124.e7. [PMID:25769911]

37. Lal S, Malhotra S, Gribben D, Hodder D. (1984) Nedocromil sodium: a new drug for the management of bronchial asthma. Thorax, 39 (11): 809-12. [PMID:6150563]

38. Lheureux S, N'Diaye M, Blanc-Fournier C, Dugué AE, Clarisse B, Dutoit S, Giffard F, Abeilard E, Briand M, Labiche A et al.. (2015) Identification of predictive factors of response to the BH3-mimetic molecule ABT-737: an ex vivo experiment in human serous ovarian carcinoma. Int. J. Cancer, 136 (5): E340-50. [PMID:25066666]

39. 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]

40. 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]

41. Martin JH, Huang TT, Fairhurst JL, Papadopoulos NJ. (2009) Cytokine specific immunoglobulin for use in diagnosis, prevention and treatment ,of cell proliferative, inflammatory, allergic, respiratory, autoimmune and arthritic disorders. Patent number: US7608693. Assignee: Regeneron Pharmaceuticals, Inc.. Priority date: 02/10/2006. Publication date: 27/10/2009.

42. Masferrer JL, Zweifel BS, Hardy M, Anderson GD, Dufield D, Cortes-Burgos L, Pufahl RA, Graneto M. (2010) Pharmacology of PF-4191834, a novel, selective non-redox 5-lipoxygenase inhibitor effective in inflammation and pain. J. Pharmacol. Exp. Ther., 334 (1): 294-301. [PMID:20378715]

43. Maurer M, Weller K, Bindslev-Jensen C, Giménez-Arnau A, Bousquet PJ, Bousquet J, Canonica GW, Church MK, Godse KV, Grattan CE et al.. (2011) Unmet clinical needs in chronic spontaneous urticaria. A GA²LEN task force report. Allergy, 66 (3): 317-30. [PMID:21083565]

44. Mazur M, Olczak J, Olejniczak S, Koralewski R, Czestkowski W, Jedrzejczak A, Golab J, Dzwonek K, Dymek B, Sklepkiewicz PL et al.. (2018) Targeting Acidic Mammalian chitinase Is Effective in Animal Model of Asthma. J. Med. Chem., 61 (3): 695-710. [PMID:29283260]

45. Mease PJ, Genovese MC, Greenwald MW, Ritchlin CT, Beaulieu AD, Deodhar A, Newmark R, Feng J, Erondu N, Nirula A. (2014) Brodalumab, an Anti-IL17RA Monoclonal Antibody, in Psoriatic Arthritis. N. Engl. J. Med., 370 (24): 2295-2306. [PMID:24918373]

46. Motawi TM, Bustanji Y, El-Maraghy SA, Taha MO, Al Ghussein MA. (2013) Naproxen and cromolyn as new glycogen synthase kinase 3β inhibitors for amelioration of diabetes and obesity: an investigation by docking simulation and subsequent in vitro/in vivo biochemical evaluation. J. Biochem. Mol. Toxicol., 27 (9): 425-36. [PMID:23784744]

47. Mukhopadhyay S, Sypek J, Tavendale R, Gartner U, Winter J, Li W, Page K, Fleming M, Brady J, O'Toole M et al.. (2010) Matrix metalloproteinase-12 is a therapeutic target for asthma in children and young adults. J. Allergy Clin. Immunol., 126 (1): 70-6.e16. [PMID:20546881]

48. Murata Y, Song M, Kikuchi H, Hisamichi K, Xu XL, Greenspan A, Kato M, Chiou CF, Kato T, Guzzo C et al.. (2015) Phase 2a, randomized, double-blind, placebo-controlled, multicenter, parallel-group study of a H4 R-antagonist (JNJ-39758979) in Japanese adults with moderate atopic dermatitis. J. Dermatol., 42 (2): 129-39. [PMID:25491792]

49. Neighbour H, Boulet LP, Lemiere C, Sehmi R, Leigh R, Sousa AR, Martin J, Dallow N, Gilbert J, Allen A et al.. (2014) Safety and efficacy of an oral CCR3 antagonist in patients with asthma and eosinophilic bronchitis: a randomized, placebo-controlled clinical trial. Clin. Exp. Allergy, 44 (4): 508-16. [PMID:24286456]

50. Oh CK, Leigh R, McLaurin KK, Kim K, Hultquist M, Molfino NA. (2013) A randomized, controlled trial to evaluate the effect of an anti-interleukin-9 monoclonal antibody in adults with uncontrolled asthma. Respir. Res., 14: 93. [PMID:24050312]

51. Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, Humbert M, Katz LE, Keene ON, Yancey SW et al.. (2014) Mepolizumab treatment in patients with severe eosinophilic asthma. N. Engl. J. Med., 371 (13): 1198-207. [PMID:25199059]

52. Padron E, Painter JS, Kunigal S, Mailloux AW, McGraw K, McDaniel JM, Kim E, Bebbington C, Baer M, Yarranton G et al.. (2013) GM-CSF-dependent pSTAT5 sensitivity is a feature with therapeutic potential in chronic myelomonocytic leukemia. Blood, 121 (25): 5068-77. [PMID:23632888]

53. Parker JM, Oh CK, LaForce C, Miller SD, Pearlman DS, Le C, Robbie GJ, White WI, White B, Molfino NA et al.. (2011) Safety profile and clinical activity of multiple subcutaneous doses of MEDI-528, a humanized anti-interleukin-9 monoclonal antibody, in two randomized phase 2a studies in subjects with asthma. BMC Pulm Med, 11: 14. [PMID:21356110]

54. Pettipher R, Vinall SL, Xue L, Speight G, Townsend ER, Gazi L, Whelan CJ, Armer RE, Payton MA, Hunter MG. (2012) Pharmacologic profile of OC000459, a potent, selective, and orally active D prostanoid receptor 2 antagonist that inhibits mast cell-dependent activation of T helper 2 lymphocytes and eosinophils. J. Pharmacol. Exp. Ther., 340 (2): 473-82. [PMID:22106101]

55. Phua EJ, Lopez X, Ramus J, Goldfine AB. (2013) Cromolyn sodium for insulin-induced lipoatrophy: old drug, new use. Diabetes Care, 36 (12): e204-5. [PMID:24265375]

56. 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]

57. Rothenberg ME, Wen T, Greenberg A, Alpan O, Enav B, Hirano I, Nadeau K, Kaiser S, Peters T, Perez A et al.. (2015) Intravenous anti-IL-13 mAb QAX576 for the treatment of eosinophilic esophagitis. J. Allergy Clin. Immunol., 135 (2): 500-7. [PMID:25226850]

58. Scheerens H, Arron JR, Zheng Y, Putnam WS, Erickson RW, Choy DF, Harris JM, Lee J, Jarjour NN, Matthews JG. (2014) The effects of lebrikizumab in patients with mild asthma following whole lung allergen challenge. Clin. Exp. Allergy, 44 (1): 38-46. [PMID:24131304]

59. Schierle S, Flauaus C, Heitel P, Willems S, Schmidt J, Kaiser A, Weizel L, Goebel T, Kahnt AS, Geisslinger G et al.. (2018) Boosting Anti-Inflammatory Potency of Zafirlukast by Designed Polypharmacology. J. Med. Chem., 61 (13): 5758-5764. [PMID:29878767]

60. Seymour JF, Kipps TJ, Eichhorst B, Hillmen P, D'Rozario J, Assouline S, Owen C, Gerecitano J, Robak T, De la Serna J et al.. (2018) Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. N. Engl. J. Med., 378 (12): 1107-1120. [PMID:29562156]

61. Smith DA, Minthorn EA, Beerahee M. (2011) Pharmacokinetics and pharmacodynamics of mepolizumab, an anti-interleukin-5 monoclonal antibody. Clin Pharmacokinet, 50 (4): 215-27. [PMID:21348536]

62. Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J, Dayton BD, Ding H, Enschede SH, Fairbrother WJ et al.. (2013) ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat. Med., 19 (2): 202-8. [PMID:23291630]

63. 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]

64. Sykes D, Bradley M, Riddy D, Willard L, Powell-Herlaar E, Sandham D, Watson S, Bauer C, Dubois G, Charlton S. (2014) QAW039, a slowly dissociating CRTh2 antagonist with potential for improved clinical efficacy. Eur. Respir. J., 44 (Supl 58): 4074.

65. Thurmond RL, Chen B, Dunford PJ, Greenspan AJ, Karlsson L, La D, Ward P, Xu XL. (2014) Clinical and preclinical characterization of the histamine H(4) receptor antagonist JNJ-39758979. J. Pharmacol. Exp. Ther., 349 (2): 176-84. [PMID:24549371]

66. Thurmond RL, Greenspan A, Radziszewski W, Xu XL, Miao Y, Chen B, Ge T, Zhou B, Baker DG, Pavlova D et al.. (2016) Toreforant, A Histamine H4 Receptor Antagonist, in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy: Results of 2 Phase II Studies. J. Rheumatol., 43 (9): 1637-42. [PMID:27422891]

67. Tian BP, Xia LX, Bao ZQ, Zhang H, Xu ZW, Mao YY, Cao C, Che LQ, Liu JK, Li W et al.. (2017) Bcl-2 inhibitors reduce steroid-insensitive airway inflammation. J. Allergy Clin. Immunol., 140 (2): 418-430. [PMID:28043871]

68. Tocker J, Mehlin C, Lim AC. (2010) Neutralizing determinants of IL-17 Receptor A and antibodies that bind thereto. Patent number: US7767206. Assignee: Amgen Inc.. Priority date: 02/10/2006. Publication date: 03/08/2010.

69. Tsitoura D, Ambery C, Price M, Powley W, Garthside S, Biggadike K, Quint D. (2015) Early clinical evaluation of the intranasal TLR7 agonist GSK2245035: Use of translational biomarkers to guide dosing and confirm target engagement. Clin. Pharmacol. Ther., 98 (4): 369-80. [PMID:26044169]

70. 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]

71. Van Eerdewegh P, Little RD, Dupuis J, Del Mastro RG, Falls K, Simon J, Torrey D, Pandit S, McKenny J, Braunschweiger K et al.. (2002) Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness. Nature, 418 (6896): 426-30. [PMID:12110844]

72. Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, Wang L, Kirkesseli S, Rocklin R, Bock B et al.. (2013) Dupilumab in persistent asthma with elevated eosinophil levels. N. Engl. J. Med., 368 (26): 2455-66. [PMID:23688323]

73. Witham J, Valenti MR, De-Haven-Brandon AK, Vidot S, Eccles SA, Kaye SB, Richardson A. (2007) The Bcl-2/Bcl-XL family inhibitor ABT-737 sensitizes ovarian cancer cells to carboplatin. Clin. Cancer Res., 13 (23): 7191-8. [PMID:18056200]