Edatrexate (10-ethyl-10-deazaaminopterin or 10-EDAM) is an analog of methotrexate with improved pre-clinical antitumor activity, more selective cellular uptake, and with the more extensive formation of intracellular polyglutamate metabolites. This drug is a new dihydrofolate reductase inhibitor, which was studied in phase II clinical trial for the patients with different cancers. The studies were discontinued, for example, in advanced renal cell carcinoma edatrexate in the investigated dose and schedule had minimal activity and was toxic. In case of non-small-cell lung cancer, the dosing schedule of edatrexate did not appear to be improved compared to other chemotherapeutic regimens. In addition, edatrexate was involved in the experiment for the treatemnt of rheumatoid arthritis, but this study was also discontinued.

ITANOXONE is a hypolipidemic and hypouricemic compound with moderate anti-inflammatory activity.

Veliflapon (BAY X1005, DG-031) is an enantioselective inhibitor of 5-lipoxygenase activating protein, or FLAP. There are variants in the gene encoding FLAP, and the gene encoding leukotriene A4 hydrolase (LTA4H) linked to risk of heart attack. These variants appear to confer increased risk of heart attack by increasing the production of leukotriene B4 (LTB4), a potent driver of inflammation produced in atherosclerotic plaques. deCODE licensed veliflapon (BAY X1005, DG-031) from Bayer AG, which developed it originally for the treatment of asthma.

Transcrocetinate (TSC) is a novel compound that offers promise as a treatment for conditions caused by hypoxia or ischemia. Unlike crocetin, it worked well in the more severe hemorrhagic shock model. Although many of the earlier studies with TSC involved the treatment of the ischemic conditions of hemorrhagic shock in both rats and swine, a few other studies involved treating purely hypoxic situations. One study showed that TSC was capable of promoting survival in rats breathing 10% oxygen. TSC also was able to increase arterial PO2 values in a rat model of acute respiratory distress syndrome (ARDS) caused by injection of oleic acid. The drug acts via a mechanism that has not been previously exploited in a pharmaceutical. TSC increases the rate of oxygen diffusion between the erythrocytes and the tissues by altering the 'structure' of water in blood plasma. It does this by causing additional hydrogen bonds to form among the water molecules. Animal toxicology studies have demonstrated that high levels of TSC are well-tolerated, and a Phase I clinical study has shown that TSC is also safe in humans. Delayed TSC treatment improves outcomes in experimental models of both ischemic and hemorrhagic stroke. TSC may be a safe and beneficial therapeutic modality for early stroke intervention, irrespective of the type of stroke involved. Transcrocetinate is in phase III clinical trial for the treatment of glioblastoma.

Eclazolast (REV 2871 or CHBZ) is a non-disodium cromoglycate (DSCG)-like, antiallergic drug. Eclazolast is taken up by rat mast cells and human leukocytes in a specific and saturable manner. The compound can be hydrolyzed by a granule-associated enzyme in the mast cell to an ionic metabolite (REV 3579) whose in vitro profile is identical to that of DSCG. Eclazolast is a potent inhibitor of both immunologic and non-immunologic histamine release. It inhibits exocytosis by intracellularly affecting only direct Fc(epsilon)RI linked processes and not through inhibition of Ca2+ influx channels.