Dutogliptin (PHX-1149T) is a small-molecule dipeptidyl peptidase-4 (DPP-4) inhibitor for the potential oral treatment of type 2 diabetes mellitus (T2DM). DPP-4 quickly degrades the insulin secretory hormones, glucose-dependent insulinotropic peptide and glucagon-like peptide-1; thus inhibiting the degradation of these hormones is a viable treatment option for patients with T2DM. In preclinical studies, dutogliptin potently inhibited DPP-4 and, in a model of T2DM, treatment with dutogliptin improved glucose homeostasis. Pharmacokinetic analyses in animals, healthy individuals and patients with T2DM demonstrated that drug exposure increased in a dose-dependent manner. Results from phase II clinical trials indicated that once-daily dutogliptin, in combination with other oral diabetes therapies, reduces postprandial blood glucose and HbA1c levels, both indicators of successful diabetes management. The incidence of adverse events was similar in treatment and placebo groups, with slightly more headache, arthralgia, sinusitis, and dizziness occurring in the 400 mg dutogliptin group compared with placebo. Phase II clinical trial for the myocardial infarction treatment is underway.

Clorisamine is an antihistamine drug developed by Schering in the 1970s. The drug was evaluated in phase 1 clinical trial on healthy volunteers. The results show that in a therapeutic dose of 2 mg the drug did not have any effects which might lead to an impairment of driving ability.

Nolpitantium (SR-140333) is a highly selective nonpeptide antagonist of neurokinin-1 (NK1) receptor. Nolpitantium potently, selectively and competitively inhibited substance P binding to NK1 receptors from various animal species, including humans. In vitro, it was a potent antagonist in functional assays for NK1 receptors such as [Sar9, Met(O2)11]substance P-induced endothelium-dependent relaxation of rabbit pulmonary artery and contraction of guinea-pig ileum. Up to 1 mkM, Nolpitantium had no effect in bioassays for NK2 and NK3 receptors. The antagonism exerted by Nolpitantium toward NK1 receptors was apparently non-competitive, with pD2' values between 9.65 and 10.16 in the different assays. Nolpitantium also blocked in vitro [Sar9, Met(O2)11]substance P-induced release of acetylcholine from rat striatum. In vivo, Nolpitantium exerted highly potent antagonism toward [Sar9, Met(O2)11]substance P-induced hypotension in dogs, bronchoconstriction in guinea-pig) and plasma extravasation in rats. Nolpitantium was found to be effective in the modulation of the inflammatory response and airway remodeling in mice. Nolpitantium is reported to cause antagonism of the SP-induced relaxations of human isolated intralobar pulmonary arterial rings. Nolpitantium also blocked the activation of rat thalamic neurons after nociceptive stimulation. Nolpitantium has been shown to reduce the severity of inflammation in trinitrobenzene sulfonic acid-induced colitis in the rat colon. Nolpitantium inhibited mustard oil-induced plasma protein extravasations in the dorsal skin of the rat hind paw. Nolpitantium had been in some phase II clinical trials but further studies were discontinued.

Cefmepidium is a semisynthetic cephalosporin with broad antibacterial activity against penicillin-resistant strains.

LAPAQUISTAT is a squalene synthase inhibitor. It was shown to lower cholesterol levels in several animal models. It was investigated for the treatment of diabetes and hypercholesterolemia, however, its development was discontinued.

Biricodar (also known as VX-710) was developed by Vertex as a chemosensitizing agent designed to restore the effectiveness of chemotherapeutic agents in tumor multidrug resistance. The phase II trials had commenced for biricodar, in combination with chemotherapy, for five common cancer indications: breast, ovarian, soft-tissue sarcomas, small cell lung cancer, and prostate cancer. In spite of completed trials, development of biricodar was discontinued because of the adverse effects.

LANEPITANT is a selective nonpeptide antagonist for the neurokinin-1 receptor. It inhibits neurogenic dural inflammation. LANEPITANT was under development as a potential analgesic drug for the treatment of migraine, arthritis and diabetic neuropathy. However, it failed to show sufficient efficacy to support further development.

IRALUKAST, a leukotriene D4 analog, has potent peptido-leukotriene antagonist activity. It was under clinical development and in phase II clinical trials as a potential treatment for asthma.

Oximonam (also known as SQ 82,291) was developed as a monobactam antibiotic that had shown good activity against different bacteria of the family Enterobacteriaceae and Haemophilus influenzae and was no activity at all against staphylococci and against Pseudomonas aeruginosa.

Carubicin (also known as Carminomycin) is an anthracycline antineoplastic antibiotic isolated from the bacterium Actinomadura carminata. Carubicin intercalates into DNA and interacts with topoisomerase II, thereby inhibiting DNA replication and repair and RNA and protein synthesis. The drug is active against a variety of experimental tumors. Pharmacology studies in animals revealed that the drug bound largely to serum proteins and that it was widely distributed. In clinical trials The main toxic effect was myelosuppression but gastrointestinal intolerance and alopecia were also reported. Objective partial responses were seen in two of seven previously untreated patients with non-small cell lung cancer and one of three patients with squamous cell carcinoma of the head and neck previously untreated with chemotherapy.