Vadimezan (5,6-dimethyl(xanthenone-4-acetic acid), ASA404, DMXAA) is a fused tricyclic analogue of flavone acetic acid with potential antineoplastic activity. In pre-clinical mouse tumour models it was demonstrated that administration of Vadimezan rapidly leads to disruption of the existing vasculature in the tumour and consequent haemorrhagic necrosis of the tumour. This was consistent with the finding that a single dose of Vadimezan induced a prolonged reduction in the growth of xenografted tumours in animal models. The ability to disrupt the vasculature in these pre-clinical models has been attributed to a rapid induction of cytokines, particularly TNFα (tumour necrosis factor α), serotonin and nitric oxide, resulting in hemorrhagic necrosis and a decrease in angiogenesis. Despite the fact that the molecular targets for the drug remained unknown, the promising pre-clinical results led to Vadimezan being selected for clinical development. Results of Phase I trials showed some restriction of tumour blood flow within 24 h of treatment, although this was not as dramatic as seen in pre-clinical models. Unlike the animal models, there was also very little evidence for the rapid death of blood vessels or for increases in TNFα levels in human tumors. No difference in antitumour activity, cytokine induction or toxicity was observed between two parallel Phase I trials, one dosed weekly and the other dosed every 3 weeks. Therefore the drug proceeded to Phase II clinical trials, dosed every 21 days in combination with chemotherapeutic agents. These trials indicated the drug had small benefits in the treatment of non-small-cell lung cancer and prostate cancer. However, a subsequent Phase III clinical trial was not able to reproduce this response and clinical development was halted.

Quincarbate is a quinoline derivative patented by N. V. Philips' Gloeilampenfabrieken as diuretic. At 12.5 mg/kg orally in rats Quincarbate increased urine excretion by 130%.

Limiglidole belongs to the class of benzimidazole derivatives exhibiting various biological activities including inhibition of platelet aggregation and prolongation of clotting time in animal models. It inhibited platelet aggregation induced by ADP. Antithrombotic activity of hypoglycemic compound limiglidole that exhibits antiplatelet activity 2-fold exceeded activity of antiplatelet agent acetylsalicylic acid in the mouse model of systemic collagen-epinephrine thrombosis. Antithrombogenic properties of limiglidole are beneficial in the treatment of diabetes mellitus.

Ethidium is a DNA intercalating agent first discovered as and used as a veterenary trypanocide. A bromide salt is commonly used as a fluorescent tag in molecular biology. The fluorescene of ethidium bromide increased 21 fold upon binding to double-stranded RNA, 25 fold upon binding double stranded DNA. Because of the binding to DNA, ethidium bromide is a powerful inhibitor of DNA polymerase.

Terestigmine (also known as CHF-2060), a cholinesterase inhibitor, was developed for the treatment of cognition disorders in Italy. However, this study was discontinued.

LY-2090314 is a GSK-3alpha and GSK-3beta inhibitor developed by Eli Lilly. Phase 2 clinical trials of LY-2090314 as a signle agenst against acute leukemia did not show clinical benefit. LY-2090314 was studied in combination pemetrexed and carboplatin against solid tumors, and in combination with FOLFOX, gemcitabine, and nab-paclitaxel against pancreatic cancer.

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.

2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH), a chlorin-based photosensitize, is used in photodynamic therapy. It has been shown the therapeutic potential of HPPH in phase II clinical trials for the treatment of esophageal cancer. Besides, HPPH participated in clinical trials in treating patients with advanced non-small cell lung cancer that blocks the air passages. However, these studies were terminated.

Vinformide (also known as N-formylleurosine), an N-formyl analog of leurosine possesses antineoplastic activity. This drug was studied for the treatment of lymphoma, leukemia and Hodkin’s disease. However, studies were discontinued, because vinformide exerted an acute cardiotoxic side effect.

Azamulin [14-O-(5-(2-amino-1,3,4-triazolyl)thioacetyl)-dihydromutilin] is an azole derivative of the pleuromutilin class of antiinfectives. Azamulin is a selective, irreversible inhibitor of cytochrome P450 (CYP) 3A isoforms (IC50 values range from 26 to 240 nM for CYP3A4 and CYP3A4/5 from different sources). It is at least 50-fold less potent against CYP2J2 and 100-fold less effective against all other CYP isoforms. Azamulin potently blocks the hydroxylation of testosterone and midazolam by CYP3A4. Azamulin exhibited remarkable antibacterial activity against all Gram-positive pathogens including MRSA, PRSP, and VRE, except for E. faecalis.