Valategrast (R-411) is a dual-acting α4/β1 - α4/β7 integrin antagonist which underwent clinical development with Roche for the treatment of multiple sclerosis (MS) and asthma. Phase I and II studies have been conducted. It had shown good efficacy in animal disease models. Following oral administration, R-411 was rapidly and completely biotransformed into its active metabolite, RO-0270608, most of which was eliminated by biliary excretion. R-411 had shown acceptable pharmacokinetics and good safety in healthy volunteers. R-411 inhibited eosinophil and T H 2 cell excitation and survival, and inhibited eosinophil migration from blood to pulmonary tissues. The idea of combining R-411 with montelukast (leukotriene antagonist) in the pharmaceutical dosage forms, therefore, provided a therapeutic treatment that had the combined effect of reducing circulating eosinophil counts and reducing eosinophil egress into pulmonary tissues, thereby providing an early onset of bronchodilation as well as sustained anti-inflammatory effects. Valategrast had been in phase II clinical trials by Roche for the treatment of asthma and in phase I clinical trials for the treatment of multiple sclerosis (MS). However, the study had been discontinued. Development of Valategrast was discontinued for the treatment of asthma after clarification of the regulatory framework for that class of compounds.

Radafaxine (GW353162, ( )-(2S,3S)-2-(3-chlorophenyl-3,5,5-trimethyl-2-morphinol) or S,S-hydroxybupropion) is an active metabolite of bupropion. It acts as an inhibitor of the dopamine transporter. Radafaxine was investigated for the treatment of depression however, development was discontinued.

OSI-7904L is a liposomal formulation of the highly specific, noncompetitive thymidylate synthase inhibitor OSI-7904 (also known as GW1843, BW1843U89, and GS7904). The liposome formulation was developed to enhance the therapeutic index and dose schedule convenience of this potent antifolate compound. This drug was studied in phase II clinical trial in patients to treat head and neck cancer, gastroesophageal adenocarcinoma and advanced biliary cancer, but these studies were discontinued. As an example in case of OSI-7904L, was revealed that its activity was below a level of clinical relevance in advanced biliary tract cancer, providing only a small degree of disease stabilization.

MK-0873 is a novel selective phosphodiesterase-4 inhibitor, which has been in development for the treatment of chronic obstructive pulmonary disease (COPD). In preclinical studies, intravenous administration of MK-0873 produced potent, dose-dependent inhibition of antigen-induced bronchoconstriction in sensitized guinea pigs. MK-0873 protected against both the early- and late-phase bronchoconstrictor response to antigen challenge in Ascaris-sensitive sheep. In healthy volunteers, MK-0873 has been shown to be safe and generally well tolerated in single oral doses up to 6 mg and in multiple oral doses up to 4 mg for 28 days. The most commonly reported adverse events were similar to those reported in other studies with drugs in its class: i.e. headaches and gastrointestinal complaints.

Ataprost (also known as ONO-41483; OP-41483), an epoprostenol agonist, participated in phase II clinical trials in Japan for the treatment patients with heart failure and myocardial ischemia. However, these trials were discontinued.

BN-2629 (also known as SJG-136 and SG2000), a dimeric pyrrolobenzodiazepine that binds in the minor groove of DNA and produces G-G interstrand cross-links via reactive N(10)-C(11)/N(10')-C(ll') imine/carbinolamine moieties. This drug was investigated in phase II clinical trials in patients with epithelial ovarian, primary peritoneal, or fallopian tube cancer, however, these studied were terminated because of the slow accrual. In addition, BN-2629 participated in phase I/II trial in participants with advanced chronic lymphocytic leukemia and acute myeloid leukemia, but Spirogen also terminated these studies.

Rubitecan [Orathecin™] is a topoisomerase I inhibitor extracted from the bark and leaves of the Camptotheca acuminata tree, which is native to China. Rubitecan is an oral compound being developed for the treatment of pancreatic cancer and other solid tumours by SuperGen. Rubitecan binds to and inhibits the enzyme topoisomerase I and induces protein-linked DNA single-strand breaks, thereby blocking DNA and RNA synthesis in dividing cells; this agent also prevents repair of reversible single-strand DNA breaks.

Oxypurinol is an active metabolite of allopurinol and is an inhibitor of xanthine oxidase. Cardiome Pharma developed oxipurinol for the treatment of allopurinol-intolerant hyperuricemia (gout) and for the treatment of congestive heart failure. It is known, that inhibition of xanthine oxidase can improve myocardial work efficiency by sensitizing cardiac muscle cells to calcium ions, which are a key determinant of cardiac muscle function. However, all these studied were discontinued.