Aceneuramic acid (also known as N-Acetylneuraminic Acid, Neu5Ac, the UX 001 tablets) prolonged released had been filed a marketing authorization application with the European Medicines Agency by Ultragenyx in the EU for the treatment of hereditary inclusion body myopathy (HIBM), a rare, progressive muscle-wasting disease. This compound, a muscle protein stimulant, is also in phase II of the clinical trial for the treatment thrombocytopenia. In addition, recently was made studies, which had shown, that existed the significant positive correlation between serum and salivary sialic acid levels in oral squamous cell carcinoma (OSCC) patients.

Fosfructose is a cytoprotective natural sugar phosphate under development by Questcor (formerly Cypros) for the potential treatment of cardiovascular ischemia, sickle cell anemia and asthma. Fosfructose acts by stimulating anaerobic glycolysis which generates adenosine triphosphate under ischemic conditions and improve the cellular energy metabolism in ischemic and hypoperfused tissues. Hypoxia forces ischemic tissue to anaerobic glycolysis for energy, which yields two molecules of ATP per glucose in contrast to 36 molecules of ATP generated during oxidative phosphorylation . Addition of exogenous Fosfructose can produce two more molecules of ATP in an uncompensated anaerobic environment and hence facilitate the recovery of ischemia tissue. Fosfructose breaks down into glyceraldehyde-3-phosphate and dihydroxyacetone phosphate, which will further break down into two molecules of pyruvate and finally produce two molecules of ATP. Other mechanisms include inhibition of the generation of oxygen free radicals by neutrophils, stabilization of cell membranes, and maintainance of the correct xanthine dehydrogenase/oxidase ratio by preventing the depletion of phosphorylated compounds in ischemic tissues. In myocardial infarction patients, FDP can improve the hemodynamic parameters, attenuate ECG proven ischemic injury and arrhythmia, prevent ATP and creatine phosphate depletion from ischemic myocardium, reduce infarct size, and increase survival rate. Exogenously administered Fosfructose has also been proven beneficial for a variety of other ischemic organs, such as liver, kidney, bowel and even brain as a consequence of its ability to penetrate to the blood brain barrier. Fosfructose trisodium had been in phase I clinical trials for the treatment of heart transplant rejection. Fosfructose trisodium had been in phase II clinical trials for the treatment of heart failure, perioperativ eischaemia and reperfusion injury. Fosfructose trisodium had been in phase III clinical trials for the treatment of sickle cell anaemia. However, all these research has been discontinued. In China, FDP has been approved and marketed as a commercial drug.

Flubendazole is an anthelmintic that is used to treat worm infection in humans. It is available OTC in Europe. Flubendazole is registered and sold in Europe (EMEA) as Fluvermal (Johnson and Johnson, Sante Bea). A 100mg dose of Fluvermal is most commonly proscribed for treating pinwoms (Enterobius vermiculus)). This is followed by a second dose of 100mg 15-21 days later to ensure reinfection is avoided, as flubendazole does not kill pinworm eggs. 100mg taken 3 times a day for 3 days is effective against larger nematodes, but only marginally effective against tapeworms. Flubendazole was validated for its anti-proliferative efficacy in MDA-MB-231 cells. Moreover, Flubendazole induced autophagy and increased ROS production. In silico analysis and experimental validation together demonstrate that Flubendazole can target autophagy-related protein 4B (Atg4B) in MDA-MB-231 cells and induce autophagy, which may shed light on the exploration of this compound as a potential new Atg4B targeted drug for future triple-negative breast cancer (TNBC) therapy.

Carbon monoxide (CO) is a colorless, odorless, tasteless, and nonirritating but highly toxic gas generated by both natural and manufactured processes. CO displays many physiological roles in the neuronal, cardiovascular, and immune systems, as well as in the respiratory, reproductive, gastrointestinal, and urogenital apparatus, including anti‐apoptotic, anti‐inflammatory, anti‐oxidant, anti‐proliferative, and vasodilator effects. Although many pathologies, including cancer, hematological diseases, hypertension, heart failure, inflammation, sepsis, neurodegeneration, and sleep disorders, have been linked to abnormal endogenous CO metabolism and functions, CO displays therapeutic actions. CO has demonstrated therapeutic potential against a wide range of human diseases. However, development of CO as a therapeutic agent is severely impeded, primarily due to the lack of pharmaceutically acceptable delivery forms of CO. The therapeutic use of CO is based on (i) the induction or gene transfer of HO‐1, (ii) the inhalation of gaseous CO, and (iii) the use of CO‐releasing molecules (CO‐RMs). There is a large amount of broad preclinical evidence of the benefits of CO in large and small animal models. Importantly, CO is effective both as a prophylactic and as a therapeutic in diverse models, such as malaria, organ transplantation and pulmonary hypertension. Inhaled CO and CO-RMs are in development as therapeutics; inhaled CO is being tested in Phase II clinical trials for kidney transplantation and various CO-RMs are under preclinical evaluation. The precise molecular targets for CO remain unclear with a wide range of evidence for both haem and non-haem targets. A commonality revolves around the contributions of the mitochondria and alterations in cellular bioenergetics. Inhaled CO delivery can be accomplished with an innovative delivery device. In addition strong medicinal chemistry is driving CO-RM development with efforts towards tissue specificity and the appropriate pharmacokinetic and pharmacodynamic profiling. Inhaled CO has found wide applications in basic research in examining CO’s physiological and pathological roles, yet its application in human has many limitations, such as difficulty in precise dose control, lack of portability and inability for targeted delivery, among others. In order to mitigate these limitations, a family of transition metal based CO-releasing molecules (CO-RMs) have been elegantly devised, and have shown CO-associated biological outcomes both in vitro and in vivo. Proterris is developing an inhaled carbon monoxide (CO) therapy for the treatment of idiopathic pulmonary fibrosis (IPF), delayed graft function (DGF), acute kidney injury and renal fibrosis.

Idebenone is a synthetic short-chain benzoquinone and a substrate for the enzyme NAD(P)H:quinone oxidoreductase (NQO1) capable of stimulating mitochondrial electron transport and supplementing cellular energy levels. Idebenone was initially developed by Takeda Pharmaceutical Company for the treatment of Alzheimer’s disease and other cognitive defects. This has been met with limited success. The Swiss company Santhera Pharmaceuticals has started to investigate it for the treatment of neuromuscular diseases. In 2010, early clinical trials for the treatment of Friedreich’s ataxia and Duchenne muscular dystrophy have been completed. In clinical trials, Idebenone (Raxone/Catena) had a positive impact on a measurement of respiratory function (Peak Expiratory Flow, or PEF) in non-ambulatory Duchenne muscular dystrophy patients who were not taking steroids. As of December 2013 the drug is not approved for these indications in North America or Europe. It is approved for the treatment of Leber's hereditary optic neuropathy (LHON) in Europe. Idebenone (Raxone) is indicated for the treatment of visual impairment in adolescent and adult patients with Leber’s Hereditary Optic Neuropathy (LHON). Because the number of patients with Leber's hereditary optic neuropathy is low, the disease is considered ‘rare’, and Raxone was designated an ‘orphan medicine’ on 15 February 2007. Idebenone is thought to help improve production of energy by restoring mitochondrial function, thereby preventing the cellular damage and the loss of sight seen in LHON. Idebenone is a rapidly absorbed, safe and well-tolerated drug and is currently the only clinically proven treatment option for Leber's hereditary optic neuropathy (LHON) patients.

Curcumin is a bright yellow chemical produced by some plants, for example, it is the principal curcuminoid of turmeric. It is sold as a food flavoring, food colorant, herbal supplement, and cosmetic ingredient. Although curcumin has been widely studied it has not been officially endorsed for any pharmaceutical use due to issues of stability and bioavailability; although it continues to b marketed as a health supplement. Curcumin has been investigated for the treatment of a number of cancers, asthma, mucositis, schizophrenia, mild cognitive impairment, and depression.

Doconexent (Docosahexaenoic acid, DHA) is an omega-3 fatty acid that is a primary structural component of the human brain, cerebral cortex, skin, and retina. DHA is widely used as a food supplement, and is beleived to support healthy brain development in young childred, prevent cardiovascular disease and cognitive decline during Alzheimer's disease. Most of these claims, however, were not supported by clinical trials. DHA spray is used as a tanner.

Bisoctrizole (Tinosorb M) is a hybrid type sun blocking agent acting as both chemical and physical sunscreen. Bisoctrizole is a hybrid UV absorber, the only organic UV filter produced and microfine organic particles (< 200 nm), like microfine zinc oxide and titanium dioxide. Where other organic UV absorbers need to be dissolved in either the oil or water phase, bisoctrizole dissolves poorly in both. It covers both UVA and UVB range. Furthermore, it does not degrade under sunlight and is not significantly absorbed into the skin. It appear highly compatible with many other common sun blocking agents. Overall, it appears to have a good safety profile, even though current safety data are insufficient and long-term human safety studies are lacking. Unlike some other organic sunscreen actives, it shows no estrogenic effects in vitro. Bisoctrizole is not approved by the U.S. Food and Drug Administration (FDA), but is approved in the EU and other parts of the world. Bisoctrizole is highly stable and also has a stabilizing effect on other UV absorbers, particularly the UVB blocker octyl methoxycinnamate (octinoxate). Bisoctrizole appears to be relatively non-toxic and rarely causes skin irritation. As with many synthetic chemicals, it is unclear whether bisoctrizole may produce low-level skin damage or systemic effects with long-term use. Considering that bisoctrizole is stable, poorly soluble and minimally absorbed by the skin, the risks appear to be low. Still, more research is on bisoctrizole safety is needed.

Creatine is an amino acid that occurs in vertebrate tissues and in urine. It is synthesized mainly in the liver from three different amino acids: arginine, glycine, and methionine. In skeletal muscles, which store 95% of it, creatine generally occurs as phosphocreatine. The rest is stored in the brain, heart, and testes. Creatine functions as part of the cell's energy shuttle. It is excreted as creatinine in the urine.

An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. Papaverine is a vasodilating agent. Papaverine is used for the treating certain conditions that are accompanied by smooth muscle spasms (eg, blood vessel, urinary, gallbladder, or intestinal spasm). Papaverine is a nonxanthine phosphodiesterase inhibitor for the relief of cerebral and peripheral ischemia associated with arterial spasm and myocardial ischemia complicated by arrhythmias. The main actions of Papaverine are exerted on cardiac and smooth muscle. Like qathidine, Papaverine acts directly on the heart muscle to depress conduction and prolong the refractory period. Papaverine relaxes various smooth muscles. This relaxation may be prominent if spasm exists. The muscle cell is not paralyzed by Papaverine and still responds to drugs and other stimuli causing contraction. The antispasmodic effect is a direct one, and unrelated to muscle innervation. Papaverine is practically devoid of effects on the central nervous system. Papaverine relaxes the smooth musculature of the larger blood vessels, especially coronary, systemic peripheral, and pulmonary arteries. Papaverine is a potent, specific inhibitor of PDE10A. Papaverine for treatment of erectile dysfunction (ED) is excluded from coverage.