Etiprednol dicloacetate (BNP-166; ethyl-17alpha-dichloroacetoxy-11beta-hydroxyandrosta-1,4-diene-3-one-17beta-carboxylate) is a new soft steroid. The compound proved to be a dissociated glucocorticoid, showing a reduction in transactivating activity while preserving transrepressive abilities. The compound effectively decreased cytokine production in lipopolysaccharide-stimulated lymphocytes and attenuated lectin-induced proliferation of blood mononuclear cells in tissue culture. The significant local effect of the compound will very likely be accompanied by a drastically reduced systemic activity indicating an encouraging selectivity of the pharmacological action of etiprednol dicloacetate. Etiprednol dicloacetate had been in a clinical trial for the treatment of allergic rhinitis, asthma and Crohn's disease. However, development has been discontinued.

Dazmegrel [UK 38485] is a thromboxane synthetase inhibitor which was undergoing development in the treatment of thrombosis, ischaemic heart disease, arrhythmias and asthma. Pfizer were conducting phase II studies in Denmark and the UK, phase I studies in Germany and Italy, and preclinical studies in France. Later this research was discontinued.

Emodin is a naturally occurring anthraquinone present in the roots of numerous plants and lichens and an active ingredient of various Chinese herbs. Emodin possesses various biological properties and serves as an anti-bacterial and anti-inflammatory agent. Emodin was studied as a potential anti-cancer agent: e.g., it was shown, that compound inhibits the invasion and migration of colon cancer cells in vitro and in vivo by blocking EMT, which is related with the inhibition of Wnt/β-catenin signaling pathway. Besides, emodin effectively ameliorates asthmatic airway inflammation and alternatively activated macrophages (AAMs) polarization, and thus can be a potential agent for the treatment of asthma. It is known that the Inhibition of AAMs is an alternative therapeutic strategy for treating asthma. Some experiments have revealed that emodin can be a beneficial dietary supplement in prolonging lifespan.

Tomelukast (previously known as LY171883), an orally active antagonist of the CysLT1 receptor (leukotriene D4), which was investigated to treat asthma, but this study was discontinued because of adverse gastrointestinal effect.

PGD2 (Prostaglandin D2) is a major cellular regulator, has been shown to bind different receptors: D prostanoid receptor (DP) and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). PGD2 reportedly inhibits platelet aggregation, the proliferation of cells, and activation of neutrophils. This compound is also a potent vasodilator that also relaxes smooth muscle but causes contraction of the bronchial airways. PGD2 promotes T cell migration via CRTH2 and aggravates asthma. In contrast, there have been some studies suggesting that PGD2 exerts anti-inflammatory effects via DP, such as inhibiting the migration and activation of neutrophils, basophils, dendritic cells and T cells. Elevated levels of prostaglandin D2 (PGD2) have been shown to be present in the bald scalp of androgenic alopecia (AGA) patients and was suggested the PGD(2)-GPR44 pathway as a potential target for treatment. Also was revealed, that PGD2 might be a new target for asthma therapy, PGD2 in serum and BALF were lower in the treated group than in the untreated group.

Khelloside is a component of Ammi visnaga L. fruits extract, a medicine which is used in Egypt as remedy for the treatment of kidney stones. Khelloside itself exhibits a wide variety of biological activities including anti-anginal, antiatherosclerotic, lipid altering, antipyretic and spasmolytic. It was clinically tested for asthma, angina pectoris and skin disease, however its develoment seems to be discontinued.

Protocatechuic acid (3,4-dihydroxybenzoic acid, PCA) is a simple phenolic acid. It is found in a large variety of edible plants and possesses various pharmacological activities. This bioactive compound is famous for its biological properties and pharmacological activities such as: antioxidant, antibacterial, anticancer, antiulcer, antidiabetic, antiaging, antifibrotic, antiviral, anti-inflammatory, analgesic, antiatherosclerotic, cardiac, hepatoprotective, neurological and nephroprotective. The neuroprotective effects of PCA, extracted from Alpinia oxyphylla, on H2O2 resulted in apoptosis and oxidative stress in cultured PC12 cells. Apoptotic cell death by H2O2 was dose-dependent. Enhanced effect of PCA on protecting PC12 cells against apoptosis, augmented glutathione (GSH) level and an increase in catalytic activity was investigated by flow cytometric analysis. In cytotoxic assays, PCA causes cell death in HepG2 cancerous cell line of liver showing that PCA stimulates the c-Jun N-terminal kinase (JNK) and p38 subgroups of the mitogen-activated protein kinase (MAPK) family. Treatment with PCA decreased OVA-induced airway hyper-responsiveness to inhaled methacholine. Cell inflammation and mucus hypersecretion was also decreased by PCA. Thus, PCA can be useful for treating asthma. Experimental studies strongly support the role of protocatechuic acid in the prevention of neurodegenerative processes, including Alzheimer's and Parkinson's diseases, due to its favorable influence on processes underlying cognitive and behavioral impairment, namely accumulation of the β-amyloid plaques in brain tissues, hyperphosphorylation of tau protein in neurons, excessive formation of reactive oxygen species and neuroinflammation.

TM30089 is a slective CRTH2 antagonist. TM30089, displayed high selectivity for and antagonistic potency on mouse CRTH2 but lacked affinity to TP and many other receptors including the related anaphylatoxin C3a and C5a receptors, selected chemokine receptors and the cyclooxygenase isoforms 1 and 2 which are all recognized players in allergic diseases. Furthermore, TM30089 and ramatroban, the latter used as a reference herein, similarly inhibited asthma pathology in vivo by reducing peribronchial eosinophilia and mucus cell hyperplasia.

CDP 840 hydrochloride is a potent and selective inhibitor of phosphodiesterase 4 (PDE4). This compound competitively inhibits all PDE4 isoenzymes, which in turn prevents the cleavage of phosphodiester bonds found in secondary messenger molecules. CDP-840 had been in phase II clinical trials for the treatment of asthma. However, CDP840 did not lead to changes in baseline forced expiratory volume in one second (FEV1) as compared to placebo. CDP 840 research has been discontinued.

HMR 1031 is a potent and specific antagonist of the integrin VLA-4 (alpha4beta1) binding to vascular cell adhesion molecule-1 (VCAM-1) and fibronectin. HMR 1031 is an inhaled drug being developed for the treatment of asthma using an Ultrahaler dry-powder inhalation device. The interaction of VLA-4 with VCAM-1 is involved in the extravasations, activation, and extravascular survival of mononuclear leukocyte and eosinophil cell types at sites of airway inflammation. Thus, the VLA-4 antagonist, HMR 1031, has potential as an anti-inflammatory agent.