Asthma

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Asthma

Disease ID:	1184
Name:	Asthma
Associated with:	7 targets
	6 immuno-relevant targets
	78 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

Key to terms and symbols

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.

epidermal growth factor receptor
Role:	Although EGFR signalling is an important pathway in bronchial epithelial repair, its dysregulation has been implicated in the pathogenesis of asthma (Holgate, 2000). Over-expression of EGFR and its ligands by airway epithelial cells have been seen in patients with asthma in relation to disease severity (Amishima et al., 1998; Enomoto et al., 2009). There is also evidence that the asthmatic airway epithelium challenged with EGF can enhance the production of pro-survival and pro-migratory factors for neutrophils that may contribute to airway mucosal inflammation in severe asthma (Uddin et al., 2013).
References:	3,23,39,85

Ligands

Key to terms and symbols

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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 [12]. 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 [17]. \| View biological activity
risankizumab
Immuno Disease Comments: Phase 2 clinical candidate for asthma (see NCT02443298). Clinical Use: Results from the first-in-human proof-of-concept trial in patients with psoriasis were reported by Krueger et al. in 2015 [44]. Phase 3 trial results in psoriasis patients were published in 2018 [32]. FDA and EMA approvals were granted in 2019 and it is also approved in Japan and Canada. Risankizumab therapy is indicated for patients with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy (Japan's authorisation additionally includes treatment of generalized pustular psoriasis, erythrodermic psoriasis and psoriatic arthritis). Investigations are ongoing in other autoinflammatory conditions. Click here to link to ClinicalTrials.gov's full list of risankizumab trials. In May 2022, two studies reported results from phase 3 RCTs of risankizumab for Crohn's disease [20,26]. The NCT04524611 (SEQUENCE) study is directly comparing risankizumab and ustekinumab in participants with moderate to severe Crohn's disease and for whom anti-TNF therapy has failed. \| View clinical data
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). 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
salmeterol
Immuno Disease Comments: Used to treat bronchospasm due to asthma. 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 RespiClick^TM or Aerivio Spiromax^TM) for the treatment of severe asthma and COPD. \| 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			80
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 3 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 [73], and offers a chemotherapy-free option for CLL patients. Venetoclax plus anti-CD20 gained FDA approval for use in adults with CLL or SLL in May 2019, based on results from the CLL14 trial (NCT02242942). \| 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 [75]. \| 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 [83], and results from NCT02446613 reported in [22]. \| 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) [10]. 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 [83]. 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 [9]. An EC₅₀ of ~4.5nM for IFNα production in PBMCs is reported [9]. \| 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) [60]. \| View clinical data
compound 7f [PMID: 29283260]			55
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) [55]. \| 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 [50]. 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 [40]. 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 [68], 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 [50]. \| View biological activity
abrezekimab
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. Ozurdex® has EMA authorisation as a treatment for macular edema and uveitis, and Neofordex® can be used to treat multiple myeloma. SARS-CoV-2 infection (COVID-19): On June 16th 2020, it was reported that results from the UK recovery trial have shown a clear survival benefit of low-dose dexamethasone in COVID-19 patients with severe respiratory complications. It cut the risk of death by a third for patients on ventilators and by 20% for those on oxygen [67]. This disclosure is preliminary, and pending peer review and publication. \| 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
JNJ-10311795
Immuno Disease Comments: An experimental dual inhibitor of the leukocyte proteases cathepsin G and chymase with potential anti-inflammatory activity.
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) [71]. \| View biological activity
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: EMA approval covers beclometasone dipropionate in fixed dose combinations with and that can be used to manage chronic obstructive pulmonary disease (COPD). It may also be used as a monotherapy to control the symptoms of asthma and allergic rhinitis in other jurisdictions. \| 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
montelukast
Immuno Disease Comments: Leukotriene receptor antagonist approved for the treatment of asthma. Clinical Use: Used in the treatment of asthma. \| View clinical data
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® Sensimist^TM 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
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) [13], 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: Oral roflumilast is used to treat asthma and chronic obstructive pulmonary disease (COPD) [41]. 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 [47]. \| 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
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) [49], inflammatory skin disorders, allergic rhinitis and in an extended release formulation, ulcerative colitis [34]. 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 asthma. Clinical Use: Indacaterol is a very long-acting, rapid onset β₂-adrenoceptor agonist [15] 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) [84] and asthma [36]. 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 (M_1-5) [76]. \| 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 210 nM, compared to 1.75 nM for the active metabolite, desisobutyrylciclesonide. K_i values show the same pattern of higher affinity of desisobutyrylciclesonide (37 nM for ciclesonide vs 0.31 nM for desisobutyrylciclesonide) [8]. SARS-CoV-2: Ciclesonide is able to block SARS-CoV-2 replication in vitro, with an EC₉₀ concentration of 6.3 μM [53] (note that this data is from a preprint article posted to bioRxiv, so has not been certified by peer review). This effect is predicted to occur through inhibition of the virus' nonstructural protein (NSP) 15. In the same assay , and algestone also inhibited SARS-CoV-2 replication, whereas , , and did not. \| 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
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 2I), moderate to severe plaque psoriasis (Phase 2I) and asthma (Phase 2) are ongoing. Encouraging results from a Phase 2 study have been reported [56]. \| View clinical data Bioactivity Comments: BLAST searches using the peptide sequences of the heavy and light chains of brodalumab link to patent US7767206 [81], and monoclonal antibody clone AM_H14/AM_L14. \| View biological activity
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 2 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
nedocromil
Immuno Disease Comments: Inhalation mast cell stabiliser used to treat asthma. Clinical Use: Used as an inhlation drug to alleviate bronchconstriction in asthma [46], 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. Clinical use in asthma has largely been replaced by the more convenient leukotriene receptor antagonists. \| 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
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 [18]. 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. Lebrikizumab was redirected for inflammatory skin conditions. The FDA rejected a Biologics License Application (BLA) for lebrikizumab for the treatment of atopic dermatitis in late 2023, but the EMA approved its use for this indication in November 2023. \| 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% [70]. The development of lebrikizumab is covered by patent US7674459, in which it appears to be the monoclonal designated as 228B/C-1 [29]. 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
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 2 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 3 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 foa asthma as it showed no benefit over placebo in their STRATOS 2 and TROPOS late-stage asthma trials [1]. The EMA approved LEO Pharma's tralokinumab product Adtralza® in July 2021, as a treatment for severe atopic dermatitis that cannot be controlled by topical drugs. FDA approval for this indication followed at the end of 2021. \| View clinical data
reslizumab
Immuno Disease Comments: Approved therapeutic as maintenance treatment for asthma in combination with other asthma medications. Clinical Use: A Phase 3 clinical trial of reslizumab as a treatment for eosinophilic asthma (NCT01287039) has been completed, and results are published in [19]. 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
dupilumab
Immuno Disease Comments: Approved drug for asthma (FDA approval in October 2018). Clinical Use: Dupilumab was originally evaluated as a treatment for atopic allergic conditions, including asthma [87], atopic dermatitis (AD) and nasal polyposis [5]. A list of trials registered at ClinicalTrials.gov is available here. The first full regulatory approval for dupilumab was granted by the FDA in March 2017 and this was for the treatment of moderate-to-severe eczema (atopic dermatitis). The EMA granted this same approval in August 2017. In October 2018, FDA approval was expanded to encompass the treatment of patients with eosinophilic type or oral corticosteroid-dependent moderate-to-severe asthma. June 2019 saw FDA approval expanded to include treatment of patients with uncontrolled chronic rhinosinusitis with nasal polyposis. \| View clinical data Bioactivity Comments: Affinity data in the table below is taken from patent US7608693 [51], using antibody clone H4H098P as a representative example of the embodiment of the patent. The clone becoming dupilumab is not reported. \| View biological activity
mepolizumab
Immuno Disease Comments: Approved therapeutic for severe eosinophilic asthma. Clinical Use: Mepolizumab is approved for the treatment of severe asthma in patients who are already taking other asthma medications [7,63]. 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. Click here to link to ClinicalTrials.gov's full list of mepolizumab trials, including ongoing trials in additional eosinophilic conditions. \| View clinical data Bioactivity Comments: In monkey studies mepolizumab decreased eosinophil count with an IC₅₀ of 1.43 μg/ml, and exhibited a half-life of ~14.5 days [90]. \| View biological activity
benralizumab			21
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 [24]. Results from Phase 3 clinical trial NCT01914757 are published in [28]. 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 [11]. 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) [25]. \| View biological activity
navarixin
Immuno Disease Comments: Completed Phase 2 clinical trial NCT00632502 for asthma. 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
dectrekumab
Immuno Disease Comments: Phase 2 trial NCT01479595 in asthma has been completed. Clinical Use: Dectrekumab (QBX258) reached Phase 2 clinical trial as a potential biologic therapy for several immune conditions, including idiopathic pulmonary fibrosis (IPF), asthma, eosinophilic esophagitis [69] (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: Evauation of tezepelumab was continued in patients with severe asthma, but it failed to demonstrate efficacy in atopic dermatitis [2]. Tezepelumab was granted breakthrough designation by the FDA in September 2018 based on data from the Phase 2b PATHWAY study. Click here to link to ClinicalTrials.gov's full listing of tezepelumab (research coded AMG 157 or MEDI9929) trials. The FDA granted full approval as a therapeutic option for severe asthma in December 2021. \| View clinical data
enokizumab
Immuno Disease Comments: Clinical candidate for asthma (maximum Phase 2). Clinical Use: Enokizumab has been evaluated in Phase 2 clinical trials as a potential anti-asthmatic therapy [61,65]. Click here to link to ClinicalTrials.gov's full listing of Phase 2 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 2 clinical trial for uncontrolled asthma, whereas a Phase 2 study in patients with inadequately controlled rheumatoid arthritis has been terminated. A Phase 1 trial in patients with previously treated chronic myelomonocytic leukemia (CMML) is ongoing [64]. SARS-CoV-2 and COVID-19:Lenzilumab has been entered into clinical trial to determine if blocking GM-CSF signalling can help to alleviate the immune-mediated cytokine release syndrome in patients with severe or critical COVID-19 pneumonia. The aim would be reduce the time to recovery in hospitalised patients. \| 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 [59] 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 [78]. \| View biological activity
fevipiprant
Immuno Disease Comments: Phase 3 clinical candidate for Asthma. Clinical Use: Phase 2I clinical trials evaluating QAW039 in asthma patients (NCT02555683 and NCT02563067) are registered with ClinicalTrials.gov. Phase 2 trial results are published in [31] 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 [77]. \| View biological activity
QAV680
Immuno Disease Comments: Completed Phase 2 trial in asthma (see NCT00814216). Clinical Use: QAV680 reached Phase 2 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 2 clinical trials were underway to evaluate the potential of QGE031 as a treatment for asthma and chronic spontaneous urticaria [54]. As of May 2021, the asthma studies had been terminated, duw to alck of efficacy. Ligelizumab failed to demonstrate superiority over placebo or [82]. Evaluation in chronic urticaria has progressed to Phase 3. \| 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). A fixed-dose combination of //mometasone furoate (QVM149, Enerzair® Breezhaler®) has completed Phase 3 evaluation as a once-daily therapy for uncontrolled asthma [30]. Results confirmed non-inferiority to twice-daily / high-dose + , and using a medium-dose had comparable efficacy but at a corresponding lower steroid dose. \| View clinical data
PF-04191834
Immuno Disease Comments: No progress beyond Phase 2 trial. Clinical Use: A Phase 2 clinical trial evaluating the brochodilatory effect of a single dose of PF-04191834 in patients with asthma has been completed. A Phase 2 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 [52]. \| 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 [35]. 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 [79]. 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 [66]. It does not antagonise ligand binding at any of the other prostanoid receptors [66]. \| View biological activity
velsecorat
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). However, AstraZeneca has terminated this drug programme. \| View clinical data Bioactivity Comments: AZD7594 transrepresses transctiption of GR-induced genes with an IC₅₀ of 55nM [38]. \| 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 [6]. 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) [4]. 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 [37]. 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]			43
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			80
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 2 clinical trial investigating its effects on ex vivo ovarian cancer samples from patients [42,48,88]. \| View clinical data
AZD1981
Immuno Disease Comments: Phase 2 clinical candidate with predicted anti-asthmatic activity (see NCT00758589 for example). Has also completed Phase 2 clinical trials for COPD (NCT00690482) and chronic idiopathic urticaria (NCT02031679). Clinical Use: AZD1981 has completed Phase 2 clinical evaluations in patients with asthma [45,72], COPD [74] and chronic idiopathic urticaria [62]. Click here to link to ClinicalTrials.gov's full list of AZD1981 studies. \| View clinical data Bioactivity Comments: Data for 48 analogues from the reference given are listed in PubChem BioAssay 630011 \| View biological activity
IL-6			27,57,85,89
Immuno Disease Comments: IL-6 is an important regulator of immune responses and has been implicated in the pathogenesis of asthma. Genome-wide association studies have revealed that genes specific to IL-6 signalling are associated with an increased asthma risk (Ferreira et al., 2011). Increased levels of IL-6 have been reported in the serum of patients with asthma (Yokoyama et al., 1995). Sputum concentrations of IL-6 show an inverse relationship with lung function in asthmatics (Morjaria et al., 2011). Elevated lung epithelial IL-6 levels have been detected in asthmatic patients with increasing disease severity and are probably a characteristic of the pathobiological processes in mucosal airway inflammation in severe asthma (Uddin et al., 2013).

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Asthma

GtoPdb Disease Summaries

Targets

GtoPdb Disease Summaries - Targets

Ligands

GtoPdb Disease Summaries - Ligands

References