Plevitrexed is a rationally designed, orally bioavailable, nonpolyglutamatable quinazoline antifolate that is a selective inhibitor of thymidylate synthase with potent antineoplastic activity and the ability to overcome antifolate resistance due to decreased folylpolyglutamate synthetase activity. It also features a lower toxicity than polyglutamatable thymidylate synthase inhibitors, presumably due to a lesser cellular retention. Plevitrexed is primarily transported into the cells via reduced folate carrier and selectively binds to the folate-binding site of thymidylate synthase with high affinity. Plevitrexed was assessed and in preclinical studies against a panel of human ovarian cancer cell lines and in several phase II clinical studies for the treatment of various solid cancers including colorectal, gastric, pancreatic and ovarian cancer. The combination of plevitrexed and carboplatin is well tolerated with no significant pharmacokinetic interaction between the two drugs - antitumor activity in platinum-pretreated gynecological malignancy was demonstrated.

Pituxate is the antitussive and bronchospasmolytic agent.

GPI-1485 belongs to a class of small molecule compounds called neuroimmunophilin ligands. This class of compounds has been shown to repair and regenerate damaged nerves without affecting normal, healthy nerves. GPI-1485 binds to FK-506-binding proteins. Phase 2 studies have been conducted to assess whether GPI-1485 is able to delay or stop disease progression and improve symptoms in patients with Parkinson's disease (PD), and whether GPI-1485 can help preserve erectile function after prostatectomy.

Daporinad is an inhibitor of nicotinamide phosphoribosyltransferase (NMPRTase), an enzyme that participates in the biosynthesis of nicotinamide adenine dinucleotide (NAD+) from niacinamide (vitamin B3). Inhibition of NMPRTase may deplete energy reserves in metabolically active tumor cells and induce tumor cell apoptosis. In addition, this agent may inhibit tumor cell production of vascular endothelial growth factor (VEGF), resulting in the inhibition of tumor angiogenesis. Daporinad was investigated as a treatment of B-cell chronic lymphocytic leukemia, melanoma, and cutaneous T-cell lymphoma. Clinical trials have shown that drug has low efficacy when used alone.

Quinacainol (also known as PK 10139 or RP 54272) is a quinolinemethanol derivative patented by Pharmindustrie as an antiarrhythmic agent. Quinacainol acts as a sodium channel antagonist and demonstrated both class Ia and Ic antiarrhythmic properties. Quinacainol blocked sodium currents in a concentration-dependent manner and with a potency similar to that of quinidine. Quinacainol produces a slowing of action potential conduction, consistent with a block of sodium channels, and a slight prolongation of action potential duration, consistent with a block of potassium currents.

Tauromustine, a new taurine-based nitrosourea that was developed as an anticancer agent. Tauromustine participated in phase III clinical trial in patients with either anaplastic astrocytoma (AA) or glioblastoma (GBM) not previously treated with chemotherapy. Besides, was studied in phase III in patients with advanced colorectal cancer. Tauromustine also was used in phase II trials for the treatment of malignant glioma. However, further studies were discontinued.

Rogletimide (pyridoglutethimide) is a second-generation nonsteroidal aromatase inhibitor that has been evaluated for use in the treatment of breast cancer. Rogletimide is a structural analog of aminoglutethimide (AG), a nonspecific aromatase inhibitor. Roglemitide is slightly less potent than AG but does not inhibit the cholesterol side-chain cleavage and shows no sedative activity. However, compared to AG, it has sub-optimal aromatase inhibition and oestradiol suppression.

Oltipraz is an organosulfur compound belonging to the dithiolethione class. It acts as a schistosomicide and has been shown in rodent models to inhibit the formation of cancers in the bladder, blood, colon, kidney, liver, lung, pancreas, stomach, and trachea, skin, and mammary tissue. Oltipraz and other 1,2-dithiole-3-thiones inactivate protein tyrosine phosphatases under physiologically-relevant conditions. Clinical trials of oltipraz have failed to demonstrate efficacy and have shown significant side effects, including neurotoxicity and gastrointestinal toxicity.

Nafoxidine is a nonsteroidal antiestrogen available as an investigational agent from the Investigational Drug Branch of the National Cancer Institute. It has been used effectively in the treatment of breast cancer patients. Nafoxidine competes with endogenous estrogen for binding to specific estrogen receptors. This agent also inhibits angiogenesis in some tissues by blocking the effects of fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF); paradoxically, it may enhance angiogenesis in uterine tissue. Nafoxidine also induces oxidative stress, protein kinase C and calcium signaling.