BQ-788, a selective endothelin (ET) B-receptor antagonist, was developed by Banyu. This compound is widely used to demonstrate the role of ET-1 and ET(B) receptor subtypes in physiological and/or pathophysiological conditions. BQ-788 was studied against hypertension. However, this study was discontinued. Besides, was shown that BQ788 could protect against brain edema by inhibiting vascular endothelial growth factor-A-mediated decrease in claudin-5. The intralesional applications of BQ788 were well tolerated and showed signs of directly and indirectly reducing the viability of melanoma cells.

Temocillin was marketed by Beecham Pharmaceuticals in the UK in the 1980s but achieved little commercial success and was withdrawn, though it remained available via the manufacturer’s medical department. Presently licensed to Eumedica, temocillin is being re-launched in the UK and Belgium for treating UTI, sepsis, and respiratory infections by ESBL (Extended-spectrum beta-lactamases) and AmpC-producing Enterobacteriaceae. It acts by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls. It irreversibly binds to the active site of specific transpeptidases and carboxypeptidases known as Penicillin Binding Proteins (PBP), preventing peptidoglycan production.

Cridanimod (Virexxa) is a small-molecule immunomodulator and interferon inducer, which, in preliminary studies, has been shown to increase progesterone receptor expression in endometrial tissue. Restoration of progesterone receptor expression may re-sensitize endometrial tumor tissue to progestin therapy in previously unresponsive tumors. Cridanimod was originally developed by Polysan and Pharmsynthez and licensed to Xenetic Biosciences. Virexxa is currently being studied in an ongoing Phase 2 multi-national study in conjunction with progestin therapy for the treatment of endometrial cancer in women with the recurrent or persistent disease who have failed progestin monotherapy.

Cetiedil is effective potassium channel blocker used as a peripheral vasodilator to treat patients with painful crises in sickle cell anemia and pain in the extremities caused by an arterial disease. Known pharmacological properties of the drug include vascular smooth muscle relaxation, inhibition of phosphodiesterase with the consequent increase in circulating cyclic AMP concentration, blockade of the effect of bradykinin and serotonin, analgesia, inhibition of platelet aggregation and the decrease of plasma and blood viscosity and plasma fibrinogen level. The antisickling effect of cetiedil is explained mainly in the light of the changes it induces in the activities of membrane-bound ATPases and the permeability properties of the erythrocyte membrane to cations and anions.

Masitinib is a new orally administered tyrosine kinase inhibitor that targets mast cells and macrophages, important cells for immunity, through inhibiting a limited number of kinases. Based on its unique mechanism of action, masitinib can be developed in a large number of conditions in oncology, in inflammatory diseases, and in certain diseases of the central nervous system. In oncology due to its immunotherapy effect, masitinib can have an effect on survival, alone or in combination with chemotherapy. Through its activity on mast cells and consequently the inhibition of the activation of the inflammatory process, masitinib can have an effect on the symptoms associated with some inflammatory and central nervous system diseases and the degeneration of these diseases. AB Science is developing masitinib in multiple sclerosis and alzheimer's disease. Masitinib targets kinases, including c-Kit, PDGFR, and Lyn. It is used in the treatment of mast cell tumors in animals, specifically dogs. Since its introduction in November 2008 it has been distributed under the commercial name Masivet. It has been available in Europe since the second part of 2009. In the USA it is distributed under the name Kinavet.

Mifamurtide (liposomal muramyl tripeptide phosphatidylethanolamine; trade name Mepact) is an immunomodulator with antitumor effects that appear to be mediated via activation of monocytes and macrophages. After intravenous administration, mifamurtide is selectively phagocytosed by monocytes and macrophages. Cytosolic Mifamurtide specifically interacts with nucleotide-binding oligomerization domain 2 (NOD2) receptor that induces nuclear factor (NF)-kB activation and is implicated in innate immune defense. Activation of monocyte-mediated tumoricidal function was observed following in vivo treatment with mifamurtide in phase I/II clinical trials. Intravenous administration of mifamurtide inhibited tumor growth and increased survival in rodent models of lung and liver metastasis. In a large, randomized, open-label, multicenter, phase III trial, the addition of adjuvant (postoperative) mifamurtide to three- or four-drug combination chemotherapy (doxorubicin, cisplatin, and high-dose methotrexate with, or without, ifosfamide) was associated with a statistically significant improvement in overall survival in patients with newly diagnosed, high-grade, non-metastatic, resectable osteosarcoma. The pattern of outcome was generally similar in a small cohort of patients with metastatic disease who were enrolled in this trial. Mifamurtide is generally well tolerated; adverse events attributed to administration of the drug include chills, fever, headache, nausea, and myalgias. In the EU, mifamurtide is indicated in children, adolescents, and young adults for the treatment of high-grade, resectable, non-metastatic osteosarcoma after macroscopically complete surgical resection; it is administered by intravenous infusion in conjunction with postoperative multiagent chemotherapy. In the US, mifamurtide is currently an investigational agent that holds orphan drug status for the treatment of osteosarcoma.

Tilarginine is L-N-monomethyl arginine (L -NMMA), a non-selective inhibitor of nitric oxide synthase (NOS), which has been studied in the treatment of septic shock and cardiogenic shock complicating myocardial infarction. Despite strong evidence that excessive nitric oxide (NO) production plays a pivotal role in the pathogenesis of septic shock and may contribute to the pathogenesis of cardiogenic shock complicating myocardial infarction, outcome studies in these two disorders have proved disappointing. Tilarginine therapy was associated with an excess mortality, particularly at doses > 5 mg/(kg h), in septic shock, whereas the effects of a lower dose (1 mg/(kg h)) in cardiogenic shock complicating myocardial infarction were neutral. The excess mortality in patients with septic shock was almost certainly the result of unfavorable hemodynamic changes induced by Tilarginine (decreased cardiac output, increased pulmonary vascular resistance and reduced tissue oxygen delivery) whereas the lack of benefit in patients with cardiogenic shock complicating myocardial infarction may have been because the dose of Tilarginine was too low.

Ethamsylate (2,5-dihydroxy-benzene-sulfonate diethylammonium salt) is a synthetic hemostatic drug indicated in cases of capillary bleeding. Ethamsylate acts on the first step of hemostasis by improving platelet adhesiveness and restoring capillary resistance. In addition it inhibits prostaglandin biosynthesis. Well-controlled clinical trials clearly showed the therapeutic efficacy of ethamsylate in dysfunctional uterine bleeding, with the magnitude of blood-loss reduction being directly proportional to the severity of the menorrhagia. Other well-controlled clinical trials showed therapeutic efficacy of ethamsylate in periventricular hemorrhage in very low birth weight babies and surgical or postsurgical capillary bleeding.

Gusperimus is an antibiotic, isolated from cultures of the soil commensal Bacillus laterosporus. It possess immunosuppressive properties and exerts its effect through binding to heat shock proteins Hsp90 and Hsc70. Although initially, the drug was being investigated for the treatment of cancer, it recieved orphan designation for the treatment of refractory Wegener’s granulomatosis.

Amrubicin is a totally synthetic 9-aminoanthracycline anticancer drug, which is approved in Japan for the treatment of small cell and non-small cell lung cancer. Upon administration amrubicin is reduced to its C-13 hydroxy metabolite, amrubicinol. The cytotoxicity of amrubicinol in vitro is 10 to 100 times greater than that of amrubicin. Thus, the anticancer activity of amrubicin is considered to derive from this active metabolite. The mechanism of action of the drug is related to the inhibition of topoisomerase II by stabilizing the cleavable complex.