Faropenem medoxomil is an ester prodrug derivative of the beta-lactam antibiotic faropenem. The prodrug form of faropenem offers dramatically improved oral bioavailability and leads to higher systemic concentrations of the drug. Faropenem medoxomil is a broad-spectrum antibiotic that is highly resistant to beta-lactamase degradation. It was under development for the treatment of acute bacterial sinusitis, community-acquired pneumonia, acute exacerbation of chronic bronchitis, and uncomplicated skin and skin structure infections.

Perflisopent is the fluorocarbon agents that make myocardial contrast echocardiography possible with venous injection. It provides prolonged contrast for myocardial contrast echocardiography via peripheral venous administration, although the hemodynamic parameters deteriorate at high doses. It had been in phase III for the diagnostic of cardiovascular disorders. However, this development was discontinued.

4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN), a non-neurotoxic derivative of penclomidine, is under development by Dekk-Tec for the intravenous treatment of solid tumours. DM-CHOC-PEN is a cholesterol carbonate derivative of 4-demethylpenclomedine with potential antineoplastic alkylating activity. Upon intravenous administration of 4-demethylcholesteryloxycarbonylpenclomedine, the carbonium moiety binds to and alkylates DNA at the N7 guanine position, thereby causing DNA crosslinks. This prevents DNA replication, inhibits cellular proliferation and triggers apoptosis. In addition, due to its lipophilic cholesteryl moiety this agent is able to cross the blood brain barrier (BBB) and therefore can be given intravenously compared to other alkylating agents that need to be given intra-cranially. DM-CHOC-PEN has undergone a Phase I study (allowed enrollment of subjects with advanced cancer +/- CNS involvement) and is being evaluated in a Phase II trial in subjects with advanced cancer involving the brain. DM-CHOC-PEN has completed Phase I/II trials in humans with primary and secondary tumors involving the brain with success. Complete remissions in both primary astrocytoma and metastatic lung and leukemia malignancies.Impressive objective responses and improved PFS/overall survival have been observed in subjects with NSCLC involving the CNS.

Penclomedine, a synthetic pyridine derivative that has made its way to clinical trials because of the antitumor activity seen using the NCI screening program. Its mechanism of action is unknown although exists assumption that it can be metabolized to a free radical, DNA-reactive species. Penclomedine was involved in phase I clinical trial in treating patients with solid tumors or lymphoma. In this trial oral penclomedine was conducted to potentially alter the toxicity profile and to avoid the neurological side effects seen with i.v. penclomedine. The more favorable toxicity profile of penclomedine was obtained. It would seem reasonable to pursue a Phase II evaluation of p.o. penclomedine in patients with intracranial neoplasms, because central nervous system penetration appears unusually good. However, information about the further development of this drug is not available.

Metamfepramone (dimethylcathinone, dimethylpropion, and dimepropion) was synthesized by various routes in the 1930s and 1940s and clinically evaluated as anorectic as well as a treatment of hypotension and symptoms of the common cold. It was widely used for the treatment of the common cold or hypotonic conditions. Due to its stimulating properties and its rapid metabolism resulting in major degradation products such as methylpseudoephedrine and methcathinone, it has been considered relevant for doping controls by the World Anti-Doping Agency (WADA). Metamfepramone was marketed as an appetite suppressant, but was made illegal in 2006.

Dehydroascorbic acid (DHA) is an oxidized form of ascorbic acid. Ascorbic acid is transported in its oxidized form via GLUT1 across the blood-brain barrier. Dehydroascorbic acid delay low-density lipoprotein (LDL) oxidation when added before the initiation of the process, they accelerate the process if added to minimally oxidized LDL. Dehydroascorbic acid is used as biochemical markers of oxidative stress in clinical investigations. Dehydroascorbic acid has been used as a vitamin C dietary supplement.

Tributyrin is a prodrug of natural butyrate. It is a neutral short-chain fatty acid triglyceride that is likely to overcome the pharmacokinetic drawbacks of natural butyrate as a drug. Tributyrin has potent antiproliferative, proapoptotic and differentiation-inducing effects in neoplastic cells. Compared with butyrate, tributyrin has more favorable pharmacokinetics and is well tolerated. Because it is rapidly absorbed and chemically stable in plasma, tributyrin diffuses through biological membranes and is metabolized by intracellular lipases, releasing therapeutically effective butyrate over time directly into the cell. Tributyrin may, at least in part, exert its growth-reducing and differentiation-inducing effect in Caco-2 cells by an upregulation of the vitamin D receptor; this may provide a useful therapeutic approach in chemoprevention and treatment of colorectal cancer. In phase I study of the orally administered tributyrin there was no consistent increase in hemoglobin F. Peak plasma butyrate concentrations occurred between 0.25 and 3 h after dose. Development of tributyrin as an anticancer agent was discontinued.

Methylselenocysteine is a part of the mammalian physiology and is a well-tolerated, versatile and economical antiangiogenic agent. This compound participated in clinical trial to determine if vitamin supplementation with this compound could restore disruption of circadian rhythm in shift workers. The preclinical efficacy of methylselenocysteine has shown the combination of methylselenocysteine with androgen deprivation therapy can be useful for the treatment of advanced prostate cancer.

Disermolide (discodermolide) is the immunosuppressant and antineoplastic agent. The marine natural product discodermolide was first isolated in 1990 from the deep-water Caribbean sponge Discodermia dissoluta. It attacks cancer cells in a similar way to the successful cancer drug Taxol that has become the best-selling anticancer drug in history. Discodermolide is a microtubule-stabilizing agent with potential for the treatment of taxol-refractory malignancies. Discodermolide is a drug that functions as an immunosuppressant and induces G2/M phase cell-cycle arrest in lymphoid and non-lymphoid cells. The cytotoxicity of discodermolide cause cell-cycle arrest by mitosis and an important alteration at the level of microtubules. Discodermolide is a potent inducer of accelerated senescence. At present, Phase I trials with discodermolide has been discontinued as a consequence of unsafe efficacy and toxicity results.

Pyroxamide is a potent histone deacetylase (HDAC) inhibitor. Pyroxamide induced terminal differentiation in murine erythroleukemia (MEL) cells and inhibited the growth by cell cycle arrest or apoptosis in a variety of tumor cells. An accumulation of acetylated histones and increased levels of p21/WAF1 expression were detected in cancer cells and in prostate xenografts treated with Pyroxamide.