Enrasentan is an orally active mixed endothelin A/B receptor antagonist with a 100-fold greater affinity for the endothelin A receptor. In an animal model of hypertension and cardiac hypertrophy the drug has reduced blood pressure, prevented cardiac hypertrophy and preserved myocardial function. In rats with hyperinsulinemia and hypertension enrasentan normalized blood pressure and prevented cardiac and renal damage. In rats with stroke the drug reduced the ischemic area in the brain. Enrasentan had been in phase II clinical trial for the treatment of heart failure but the results suggested that enrasentan does not appear to have favorable effects on ventricular remodeling.

Gepotidacin (formerly GSK2140944) is a novel, first-in-class, triazaacenaphthylene antibacterial that selectively inhibits bacterial DNA gyrase and topoisomerase IV by a unique mechanism, one that is not utilized by any currently approved human therapeutic agent. As a consequence of its novel mode of action, gepotidacin is active in vitro against target pathogens carrying resistance determinants to established antibacterials, including fluoroquinolones. Gepotidacin has demonstrated in vitro activity against key pathogens, including drug-resistant strains, associated with a range of conventional and biothreat infections. GlaxoSmithKline is developing Gepotidacin for the treatment of gonorrhoea and skin and soft tissue infections.

Eltoprazine, a 5-HT1A/B receptor partial agonist, was created by Duphar in the 1980s (as DU-28853) and was subsequently developed by Solvay to treat pathological aggression. This drug is in clinical development for the treatment of Parkinson's disease levodopa-induced dyskinesia (PD-LID), Alzheimer's aggression and adult attention deficit hyperactivity disorder (adult ADHD). In addition, was shown, that the drug could be useful for normalizing prefrontal cognitive abilities, reducing aggression and impulsivity, and improving cognitive function in schizophrenia.

Quiflapon Sodium (MK-0591; (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-yl-methoxy)- indol-2-yl]-2,2-dimethyl propanoic acid, previously L-686,708) had been in phase II clinical studies for the treatment of inflammatory bowel disease, but the study was discontinued later, because in spite of MK-591 markedly inhibited Leukotrienes (LT) biosynthesis, it did not differ significantly from placebo in clinical efficacy. Also was discovered, that MK-0591 may modify the airway changes associated with bronchial hyper responsiveness, as well as offer symptomatic relief in asthma. MK-0591 is a selective and specific 5-Lipoxygenase-activating protein (FLAP) inhibitor with an IC50 value of 1.6 nM in a FLAP binding assay. In additional, recently was discovered, that MK591 possesses all major attributes of a standard anti-metastatic agent with significant cancer-selective effect, and suggest that MK591 may turn out to be an effective agent for therapy of castration-resistant, bone-metastatic prostate cancer. Though details of the molecular underpinnings of the anti-metastatic action of MK591 are unknown at this time, this finding gives an opportunity for further exploration to better understand the signaling mechanisms involved by in vitro and in vivo experiments.

Talibegron (ZD2079) is a β3 adrenoceptor agonist and insulin sensitiser. It was developed as a potential treatment for obesity and non-insulin-dependent diabetes mellitus. Talibegron hydrochloride had been in phase II clinical trials by AstraZeneca for the treatment of type 2 diabetes and obesity. However, this research has been discontinued.

Dactolisib is a dual inhibitor of phosphatidylinositol 3-kinase (P13K) and the downstream mammalian target of rapamycin (mTOR) by binding to the ATP-binding cleft of these enzymes (inhibitor of PI3K/Akt/mTOR cascade). It is being investigated as a possible anti-cancer cancer agent and drug against Influenza virus infections. Frequently reported adverse events included nausea, vomiting, diarrhoea, fatigue/asthenia, anaemia, and anorexia.

Forodesine hydrochloride is the salt of the synthetic high-affinity transition-state analog forodesine (BCX-1777, immucillin-H), a substrate designed to mimic the properties or the geometry of the transition state of reaction. It is an anticancer drug that has been developed for the treatment of different hematologic malignancies. In December 2006, orphan designation (EU/3/06/421) was granted by the European Commission to Napp Pharmaceuticals Research Limited, United Kingdom, for forodesine hydrochloride for the treatment of acute lymphoblastic leukemia. Forodesine hydrochloride has been evaluated in Phase I/Phase II clinical trials for several cancer types including chronic lymphocytic leukemia (CLL), B-Cell acute lymphoblastic leukemia and refractory cutaneous T-cell lymphoma (CTCL). Forodesine is a potent purine nucleoside phosphorylase (PNP) inhibitor that acts by elevating plasma 2'-deoxyguanosine (dGuo) and intracellular deoxyguanosine triphosphate, which in turn affects deoxynucleotide-triphosphate pools and induces cell death by apoptosis. Forodesine in the presence of dGuo inhibited the proliferation of CEM-SS (T-acute lymphoblastic leukemia) cells with an IC50 of 0.015 uM. This inhibition by forodesine and dGuo was accompanied by a 154-fold and 8-fold elevation of endogenous dGuo triphosphate (dGTP) and deoxyadenosine triphosphate (dATP) pools, respectively. Cytotoxic activity of forodesine in the presence of dGuo was selective to T lymphocytes. It is a 10- to 100-fold more potent inhibitor of human lymphocyte proliferation than other known PNP inhibitors such as PD141955 and BCX-34.8

Org 25935 (SCH 900435) is a synthetic drug developed by Organon International, which acts as a selective inhibitor of the glycine transporter GlyT-1. In human trial for prevention of relapse in alcohol-dependent patients in Org 25935 demonstrated no benefit over placebo in preventing alcohol relapse. Org 25935 was tested as an adjunctive treatment to atypical antipsychotics in predominant persistent negative symptoms of schizophrenia, where it did not differ significantly from placebo in reducing negative symptoms or improving cognitive functioning. Clinical trials against panic disorder did not show any benefit compared to placebo.

Filanesib is a highly selective, targeted KSP inhibitor with a mechanism of action distinct from currently available myeloma therapies such as immunomodulatory drugs (IMiDs®) and proteasome inhibitors. Across multiple studies, filanesib has demonstrated activity in heavily pretreated multiple myeloma patients, with a consistent safety profile including no drug-induced peripheral neuropathy and limited non-hematologic toxicity. Adverse events are generally limited to transient, non-cumulative and predominantly asymptomatic myelosuppression (decreases in blood counts) when supportive measures are used. Alpha 1-acid glycoprotein (AAG), a plasma protein, is a potential patient selection marker for filanesib. AAG is undergoing further investigation in clinical trials and could represent the first patient selection marker for a myeloma therapy. Filanesib is in Phase II for Multiple myeloma treatment.

Mofegiline (MDL 72,974A or (E)-2-(4-fluorophenethyl)-3-fluoroallylamine, hydrochloride), is a selective and irreversible inhibitor of monoamine oxidase type B (MAO-B) both in vitro and in vivo. In addition, mofegiline inhibits semicarbazide-sensitive amine oxidase activity from human serum and saphenous vein. In phase II studies, MDL 72,974A is proving to be a useful adjunct to conventional therapy of Parkinson's disease. It seems mofegiline development was discontinued.