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.

Canfosfamide is a modified glutathione analogue and nitrogen mustard prodrug, with potential antineoplastic activity. Canfosfamide is selectively activated by glutathione S-transferase P1-1 an enzyme that is over-expressed in many human cancers including ovarian cancer. GST P1-1-mediated cleavage leads to an active cytotoxic phosphorodiamidate alkylating metabolite that forms covalent linkages with nucleophilic centers in tumor cell DNA, which may induce a cellular stress response and cytotoxicity, and decrease tumor cell proliferation. Preclinical studies showed that canfosfamide inhibited the growth and was cytotoxic to a wide range of established cancer cell lines including those derived from ovarian cancer (OVCAR3, HEY, SK-OV-3). Canfosfamide treatment inhibited cancer cell proliferation and induced apoptosis through the activation of the cellular stress response kinase pathway. The cytotoxic activity of canfosfamide correlated with the expression of GST P1-1. Cancer cells in which GST expression levels were increased by transfection with the GST P1-1 gene, were more sensitive to the cytotoxic effects of canfosfamide than the parental cell lines Canfosfamide in combination with pegylated liposomal doxorubicin is well tolerated and active in platinum and paclitaxel refractory or resistant ovarian cancer.

Zicronapine (formerly known as Lu 31-130), an oral antipsychotic that was studied for the treatment of schizophrenia. The drug was used in a phase III clinical trial.

Sergliflozin, a novel oral selective low-affinity sodium glucose cotransporter (SGLT2) inhibitor, improves hyperglycemia by suppressing renal glucose reabsorption, in which SGLT2 participates as a dominant transporter. Its prodrug form, sergliflozin etabonate, is orally available and is converted to sergiflozin upon absorption. Development of sergliflozin has been discontinued in favor of remogliflozin.

Tilapertin (also known as AMG 747) is a piperazineacetic acid derivative patented by Amgen Inc as glycine transporter-1 inhibitor useful for the treatment of negative symptoms of schizophrenia. Oral administration of AMG 747 dose-dependently increases cerebrospinal fluid(CSF) glycine concentration in rats. In humans, Tilapertin has linear pharmacokinetics, prolonged half-life, and acceptable safety and tolerability at multiple doses up to 60 mg daily dosing. Unfortunately, in clinical trials, Tilapertin failed to demonstrate superior efficacy compare antipsychotic therapy in clinically stable people with schizophrenia.

Arno Therapeutics is developing AR-12, an orally available, targeted therapy for cancer and infectious diseases. AR-12 is a potentially first-in-class, orally available, targeted anti-cancer agent that has been shown in preclinical studies to inhibit phosphoinositide-dependent protein kinase-1, or PDK-1, a protein in the PI3K/Akt pathway that is involved in the growth and proliferation of cells, including cancer cells. Although FDA-approved drugs that target the Akt pathway have shown efficacy in treating cancer, some tumors either do not respond to these drugs or eventually become resistant to therapy. Scientists hypothesize that a combination of drugs that inhibit different targets in this pathway could provide synergistic or additive benefits to increase efficacy and potentially overcome drug resistance. For this reason, there has been particular interest within the biopharmaceutical industry in developing inhibitors of PI3K, PDK-1, and Akt. AR-12 was licensed to Arno in January 2008 by The Ohio State University Research Foundation for commercial development by Arno as a potential treatment for solid tumors and hematological malignancies. In preclinical studies, AR-12 has shown efficacy in a wide range of tumor types, including breast, lung, prostate, pancreatic, brain and hematological cancers, as both a single-agent as well as in combination with leading oncology therapeutics. Also AR-12 represents a promising class of small molecules with broad-spectrum antifungal activity. AR-12 inhibits fungal acetyl coenzyme A (acetyl-CoA) synthetase in vitro and is fungicidal at concentrations similar to those achieved in human plasma. AR-12 has a broad spectrum of activity, including activity against yeasts (e.g., Candida albicans, non-albicans Candida spp., Cryptococcus neoformans), molds (e.g., Fusarium, Mucor), and dimorphic fungi (Blastomyces, Histoplasma, and Coccidioides) with MICs of 2 to 4 ug/ml. AR-12 is also active against azole- and echinocandin-resistant Candida isolates, and subinhibitory AR-12 concentrations increase the susceptibility of fluconazole- and echinocandin-resistant Candida isolates. Also AR-12 acts as a broad-specificity anti-viral drug in vitro and in vivo. AR-12 (OSU-03012) interacts with multiple chaperone proteins of the HSP90 family and the HSP70 family resulting in a broad spectrum of chaperone inactivation. This overall loss of chaperone functionality results in cells being more readily capable of undergoing autophagic processes and in cells that have a reduced competency for virus replication.

Butopyrammonium is organic cationic compound.

PF-03654746 is a potent, selective antagonist of the human H3 receptor, developed by Pfizer. It was in the clinical trial phase II for the treatment of excessive daytime sleepiness (EDS) associated with narcolepsy, Tourette syndrome as well as potential anti-allergy applications and in phase I of clinical trial for the treatment of Schizophrenia and Alzheimer's disease, but these investigations were discontinued.

Talnetant (SB-223412) is a selective, orally active neurokinin 3 receptor antagonist and is under development for the potential treatment of several disorders, including irritable bowel syndrome, schizophrenia, chronic obstructive pulmonary disease, cough, overactive bladder and urinary incontinence. The most common adverse effects were headache, fatigue, and nausea.