Fasitibant (MEN-16132) is a non-peptide sulfonamide-containing bradykinin hB2 receptor antagonist. It inhibits pro-inflammatory response in vitro and alleviates inflammatory hyperalgesia in rodent models of osteoarthritis. Menarini Group was developing fasitibant for the treatment of osteoarthritis. Fasitibant development has been discontinued.

ABC-294640 is an orally bioavailable and selective sphingosine kinase-2 (SphK2) inhibitor with IC50 of approximately 60 uM. ABC-294640 inhibits SK2, a lipid kinase that catalyzes formation of the lipid signaling molecule sphingosine 1-phosphate (S1P). S1P promotes cancer growth, and proliferation and pathological inflammation, including TNFα signaling and other inflammatory cytokine production. Specifically, by inhibiting the SK2 enzyme, ABC-294640 blocks the synthesis of S1P which regulates fundamental biological processes such as cell proliferation, migration, immune cell trafficking and angiogenesis, and are also involved in immune-modulation and suppression of innate immune responses from T cells. Preliminary evidence suggests that because of its specificity for targeting SK2, rather than SK1, ABC-294640 may have a better therapeutic ratio than nonspecific sphingosine kinase inhibitors or those targeting only SK1. Oral administration of ABC-294640 to mice bearing mammary adenocarcinoma xenografts results in dose-dependent antitumor activity associated with depletion of S1P levels in the tumors and progressive tumor cell apoptosis. Therefore, this newly developed SK2 inhibitor provides an orally available drug candidate for the treatment of cancer and other diseases. ABC-294640 has completed multiple successful pre-clinical studies in inflammatory, GI, radioprotection and oncology models, as well as a Phase I clinical study in cancer patients with advanced solid tumors.

Efatutazone (CS-7017 or RS-5444) is a peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist with antineoplastic properties. Mediated through activation of PPAR-gamma, this agent is capable of inducing cell differentiation and apoptosis, thereby leading to a reduction in cellular proliferation. Efatutazone was in clinical trials for the treatment of solid tumors however; its development has been discontinued.

Closantel is a synthetic anti parasitic agent which is highly effective against adults and larvae (6 to weeks old) of liver flukes (Fasciola hepatica), and against several important gastrointestinal roundworms (e.g. Bunostomum, Haemonchus, Oesophagostomum, Ostertagia - Teladorsagia, Strongyloides, Trichostrongylus), as well as against screwworms (maggots of Cochliomyia spp and Chrysomya spp), sheep nasal bots (Oestrus ovis), and sheep keds (Melophagus ovinus). The molecular mode of action closantel is not completely elucidated, but closantel decouples the mitochondrial oxidative phosphorylation, which leads to the inhibition of ATP synthesis, this seems to occur through suppression of the activity of succinate dehydrogenase and fumarate reductase, two enzymes involved in this process. Finally this all cause the death of the parasite. Recently it has been discovered that closantel also inhibits chitinase in Onchocerca volvulus, a filarial nematode causing river blindness in humans. Chitinase is an enzyme involved in larval molting. Its inhibition interrupts their development to adult worms. This drug possesses some side effects: hyper acute anaphylactic reactions in cattle; hypersensitivity reactions; overdoses can cause reduced visibility or blindness, anorexia, lack of coordination and general weakness.

FENETHAZINE was a first-generation phenothiazine-derived antihistamine drug. Promethazine was derived from FENETHAZINE.

Mioflazine, a calcium antagonist, was developed as a cardioprotector. It protected a human atrial muscle against the destructive effects of high concentrations of Ca2+. Information about the current study of this agent is not available.

Avitriptan (BMS-180048), a new 5-HT 1B/1D receptor agonist, has been studied in phase II clinical trials in patients with migraine headaches. Later experiments have confirmed antimigraine activity together with coronary side-effect potential that is why further studies were discontinued.

Pirogliride is the antidiabetic agent. It has been found to produce a hypoglycemic effect in nondiabetic rats, dogs, mice, and monkeys. To being three to four times more potent than tolbutamide, pirogliride also differs from the sulfonylureas in lowering blood glucose concentrations of streptozotocin-diabetic rats and db/db mice, and, moreover, oral administration to normal fasted dogs did not produce the characteristic rise in insulin concentrations observed with tolbutamide. Pirogliride potentiates glucose-induced insulin secretion from isolated islets. This effect is accompanied by a facilitated glucose metabolism. Pirogliride partially prevents the known inhibitory effects of mannoheptulose on glucose-induced secretion and utilization. Pirogliride was found to produce a concentration-dependent inhibition of gluconeogenesis in rat kidney cortex slices. hepatocytes and perfused liver. Pirogliride was metabolized in man to a small extent by oxidation of the 4-position of the phenyl ring.