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.

Midesteine (previously known as MR 889), a thiolactic acid derivative was developed as an inhibitor of the chymotrypsin and elastolytic activity of leukocyte elastase. Midesteine participated in clinical trials for patients with chronic obstructive pulmonary disease. The drug is also studied to treat asthma, cystic fibrosis, and emphysema. However, all these studies were discontinued.

Arctigenin is a plant lignan extracted from Arctium lappa that has been shown to have estrogenic properties. In ER-positive MCF-7 cells, arctigenin efficiently inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell migration and invasion. Arctigenin confers anti-metastatic effects by inhibiting MMP-9 and uPA via the Akt, NF-κB and MAPK signaling pathways on breast cancer, regardless of ER expression. Intake of arctigenin could be an effective supplement for breast cancer patients. Arctigenin is a phenylpropanoid dibenzylbutyrolactone lignan compound possessing antitumor, anti-inflammatory, anti-influenza, antioxidant, antibacterial, and hypoglycaemic activities. Arctigenin exhibited significant antiproliferative activity against CCRF-CEM cells after 72 h treatment with IC50 values of 1.21 ± 0.15 um. It arrested CCRF-CEM cells in the S phase. It induced apoptosis in CCRF-CEM cells in a concentration- and time-dependent manner. Arctigenin is a good candidate for the development of novel agents against T-cell lymphoma. Arctigenin has been found to act as an agonist of adiponectin receptor 1 (AdipoR1). Arctigenin is an antagonist of MR and effectively decreases the Na/K-ATPase 1 gene expression, thus highlighting its potential as an anti-hypertensive drug lead compound.

AZD8055 is a new ATP-competitive mTOR kinase inhibitor that was developed to overcome the limitations of the first generation of allosteric mTORC1 inhibitors (rapamycin and its analogs) as anticancer agents. AZD8055 potently and selectively inhibits mTOR by directly targeting its catalytic site, which results in the blockade of the activity of both mTORC1 and mTORC2 complexes. It displays antitumoral activity by inhibiting proliferation and/or inducing cell death in various cancer cell models, including ovarian clear cell carcinoma.

LY404039 [(-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]-hexane-4,6-dicarboxylic acid] is an agonist of orthosteric metabotropic glutamate receptor (mGluR)2/3. In addition, it acts as an agonist at dopamine D2 receptors. LY404039 demonstrated broad antipsychotic and anxiolytic efficacy across multiple animal models. LY-2140023 is a methionine amide prodrug of LY-404039 being developed by Eli Lilly & Co for the potential oral treatment of schizophrenia.

Balicatib is a potent cathepsine K inhibitor that was developed for the treatment of knee osteoarthritis. The development of Balicatib was terminated in phase II due to the occurrence of skin rashes and rarer incidences of morphea-like skin changes.

Orvepitant is a novel generation brain penetrant, selective and potent, small molecule NK-1 receptor antagonist. Orvepitant’s (GW823296) mode of action and developability characteristics made it a suitable development candidate for the treatment of common anxiety disorders, posttraumatic stress disorder and major depressive disorder. It’s in phase II clinical trials as an effective inhibitor of itch-associated response.