TG-100115 is a potent dual inhibitor of PI3K-gamma and PI3K-delta. TG-100115 has broad anti-inflammatory activities. TG-100115 provided potent cardioprotection, reducing infarct development and preserving myocardial function. In murine models of asthma and acute stages of chronic obstructive pulmonary disease, aerosolized TG100-115 demonstrated not only markedly inhibited anti-inflammatory activity but also, in the case of the asthma model, improved functional outcome for the test animals. TG-100115 can be used as a potent TRPM7 kinase inhibitor and a potent inhibitor of breast cancer cell migration.

(R)-Mequitazine or V0162 (10-[(3R)-1-azabicyclo[2.2.2]oct-3-ylmethyl]-10H-phenothiazine) is an anticholinergic enantiomer of mequitazine, an existing oral racemic antihistamine commercialized for over 30 years. (R)-Mequitazine was found to be an antagonist at muscarinic acetylcholine receptors behaving as an inverse agonist. (R)-Mequitazine was investigated in clinical trials for the treatment of chronic obstructive pulmonary disease, asthma and urinary incontinence.

GSK-256066 is a PDE4B inhibitor which was developed by GlaxoSmithKline and tested in phase II of clinical trials for the treatment of COPD, Asthma and Seasonal allergic rhinitis. According to the GSK pipeline, development of GSK-256066 was terminated. There are studies that describes the possibility of repurposing of the drug as antitrypanosomal agents, because it inhibits PDEB1 of Trypanosoma brucei.

5-((4-(6-Chlorothieno[2,3-d]pyrimidin-4-ylamino)piperidin-1-yl)methyl)-2-fluorobenzonitrile monofumarate (PRX-08066) is a selective 5-hydroxytryptamine receptor 2B (5-HT2BR) antagonist that causes selective vasodilation of pulmonary arteries. This drug was discovered and developed by Predix (later Epix) Pharmaceuticals and is being researched for the treatment of pulmonary arterial hypertension. In animal studies, PRX-08066 has been found to reduce several key indicators of pulmonary arterial hypertension and improved cardiac output, with similar efficacy to established drugs for this condition such as bosentan, sildenafil, beraprost and iloprost.

Navarixin (SCH 527123) is an oral antagonist of CXC receptors 1 and 2. The drug is currently under Phase II trial for the treatment of psoriasis, COPD and asthma.

AZD-1981, developed by AstraZeneca, is a potent (binding IC50 of 4nM), fully reversible, functionally non-competitive antagonist of human CRTh2. It blocks agonist-induced human eosinophil CD11b expression, shape change (including in whole blood), and chemotaxis as well as an basophil shape change and Th2-cell chemotaxis at IC50's of 8.5-50nM. Potency is similar across species as is plasma protein binding (~97%). AZD-1981 is a weak (10s of μM) inhibitor in vitro of CYP2C9, OATP1B1 and UGT1A1 as well as an inducer of CYP3A4. AZD-1981 was well tolerated and no safety concerns were identified.There was no beneficial clinical effect of AZD-1981, at a dose of 1000 mg twice daily for 4 weeks, in patients with moderate to severe COPD. AZD-1981 has being discontinued for asthma and chronic obstructive pulmonary disease. AstraZeneca is collaborating with Johns Hopkins University for the development of AZD-1981 in the treatment of chronic idiopathic urticaria. It is in phase II clinicals studies for the treatment of Urticaria.

Avelestat, also known as AZD9668, is a novel, oral inhibitor of neutrophil elastase (NE), an enzyme implicated in the signs, symptoms, and disease progression in NE-driven respiratory diseases such as bronchiectasis, Cystic Fibrosis and chronic obstructive pulmonary disease via its role in the inflammatory process, mucus overproduction, and lung tissue damage. Its development was discontinued due to unknown reasons. Nevertheless, this drug in the phase II of clinical trial as adjunctive therapy in improving insulin sensitivity of insulin-resistant type 2 diabetic subjects. The drug's clinical profile suggests that it will be well tolerated with few, if any, side effects, and the existence of simple methods that can indirectly measure its activity in vivo.

Freselestat (ONO-6818) is reversible, nonpeptide high affinity and selective human neutrophil elastase inhibitor, which was under development by Ono for the potential treatment of inflammatory conditions, such as rheumatoid arthritis, inflammatory bowel disease and chronic obstructive pulmonary disease (COPD). Freselestat mediated neutrophil elastase inhibition, leads to the reduction of interleukin 8 production and the reduction of the complement membrane attack complex formation. Freselestat competitively inhibits neutrophil elastase in humans, rats, and hamsters, but does not inhibit other proteases such as pancreatic elastase, trypsin, proteinase 3, cathepsin G, or matrix metalloproteinases. Freselestat inhibits acute lung injury induced by neutrophil elastase in rats, minimizing lung hemorrhage, the accumulation of neutrophils in the lung and suppresses leukocyte levels in an in vivo model of COPD. Freselestat was in phase I studies for COPD in Japan and the US. However, due to abnormal variations in liver function, the development of Freselestat was terminated.

UK-432097 is a selective adenosine A2a agonist which was in development with Pfizer as an inhaled treatment for asthma and chronic obstructive pulmonary disease. UK-432097 had been in phase II clinical trials by Pfizer for the treatment of chronic obstructive pulmonary disease (COPD). However, this study was terminated prematurely due to futility based on results of interim analysis.

Enprofylline is a xanthine derivative that shares theophylline's bronchodilator properties. It can be considered a relatively selective, though not potent adenosine A2B receptors antagonist. Enprofylline is used in asthma, chronic obstructive pulmonary disease, and in the management of cerebrovascular insufficiency, sickle cell disease, and diabetic neuropathy. Long-term enprofylline administration may be associated with the elevation in liver enzyme levels and unpredictable blood levels.