LY-2886721 is selective and potent BACE1 inhibitor developed by Eli Lilly. It reached phase II of clinical trials against Alzheimer'd disease, but its development was suspended due to possible liver toxicity.

Scyllo-inositol (ELND005) is an inositol isoform. Inositol is a derivative of cyclohexane with six hydroxyl groups, making it a polyol. It also is known as a sugar alcohol, having exactly the same molecular formula as glucose or other hexoses. Scyllo-inositol (ELND005) is a naturally occurring plant sugar alcohol found most abundantly in the coconut palm. It appears to accumulate in a number of human tissues and biofluids through dietary consumption. It has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. Although scyllo-inositol (ELND005) at pharmacologic doses may alter myo-inositol levels and indirectly affect phosphatidyl-inositol signaling, its main effects are thought to be binding and inhibition of beta-amyloid 42 peptide aggregation and formation of beta-amyloid fibrils. In transgenic animals, scyllo-inositol (ELND005) reduced brain beta-amyloid concentrations and plaque burden, preserved synaptic density, and improved learning deficits. Scyllo-inositol (ELND005) also appears to neutralize toxic effects of beta-amyloid oligomers, including amelioration of oligomer-induced synaptic loss, long-term potentiation inhibition, and memory deficits. Scyllo-inositol (ELND005) is an attractive candidate as a potential disease-modifying oral treatment for Alzheimer disease.

Fucoxanthin isis a marine carotenoid mainly found in brown algae, giving them a brown or olive-green color. Fucoxanthin is investigated for its anti-inflammatory, antinociceptive and anti-cancer effects. In vivo studies have demonstrated that oral administration of fucoxanthin inhibited carcinogenesis in an animal model of duodenal, skin, colon and liver cancer. Fucoxanthin causes antitumor and anticarcinogenic effects by inducing G1 cell-cycle arrest and apoptosis by modulating expression of various cellular molecules and cellular signal transduction pathways, but the exact mechanism of anti-cancer action of fucoxanthin is not fully elucidated. Fucoxanthin regulates lipids metabolism, the effect most likely mediated by AMK-activated protein kinase. A clinical trial of fucoxanthin against non-alcoholic fatty liver disease is ongoing.

NGX267 is a partial muscarinic receptor agonist with functionally specific M1 and M3 receptor activity, developed by Torrey Pines Therapeutics(TPTX) for the treatment of Xerostomia, Alzheimer’s disease and cognitive deficits in schizophrenia. NGX-267 had been in phase II clinical trials for the treatment of Xerostomia, however, all researchers on this drug candidate were discontinued.

Pfizer was developing PF-4995274, an orally administered serotonin 4 receptor (5HT-4) agonist for the treatment of Alzheimer's disease. In 2011, the company discontinued the development of the compound.

Encenicline (EVP-6124; MT-4666) acts as a potent partial and selective agonist at alpha-7 nicotinic acetylcholine receptor. Encenicline significantly improved memory function in animal models. FORUM Pharmaceuticals (formerly EnVivo Pharmaceuticals) is developing encenicline for the treatment of cognition disorders such as schizophrenia and for Alzheimer's disease.

PF-04447943 is a potent, selective brain penetrant PDE9 inhibitor (Ki of 2.8, 4.5 and 18 nM) for human, rhesus and rat recombinant PDE9 respectively and high selectivity for PDE9 versus PDEs1-8 and 10-11. PF-04447943 was being developed by Pfizer for the treatment of cognitive disorders. PF-04447943 attenuates a scopolamine-induced deficit in a novel rodent attention task. PF-04447943 enhances synaptic plasticity and cognitive function in rodents. PF-04447943 has completed Phase II clinical trials in subjects with mild to moderate AD in 2013 but this research was discontinued. Pfizer completes a phase I trial in Sickle cell anaemia.

3-Indolepropionic acid (IN-OX1; Indole-3-propionic acid; OX-1; Oxigon; SHP 22; SHP-622; VP-20629), an endogenous substance produced by bacteria in the intestine, is a deamination product of Tryptophan (T947200) that protects the hippocampus (studied in gerbils) from ischemic damage and oxidative stress. It’s ability to protect the neurons in this way is attributed to its potent antioxidative effects. 3-Indolepropionic acid is also hypothesized to have protective effects on the thyroid gland. 3-Indolepropionic acid is being studied for therapeutic use in Alzheimer's disease. 3-Indolepropionic acid (IPA) completely protected primary neurons and neuroblastoma cells against oxidative damage and death caused by exposure to Abeta, by inhibition of superoxide dismutase, or by treatment with hydrogen peroxide. In kinetic competition experiments using free radical-trapping agents, the capacity of IPA to scavenge hydroxyl radicals exceeded that of melatonin, an indoleamine considered to be the most potent naturally occurring scavenger of free radicals. In contrast with other antioxidants, IPA was not converted to reactive intermediates with pro-oxidant activity. In 2011, Intellect redirected the focus of the OX1 program from Alzheimer's disease to FA (Friedreich's Ataxia). Research suggests that the symptoms associated with FA are the result of oxidative stress caused by the abnormal accumulation of iron. OX1's ability to neutralize ROS could be an effective agent to reduce oxidative stress in FA, thereby eliminating the symptoms of FA and increasing both quality of life and longevity in affected individuals.

Xanthohumol is a prenylated flavonoid most abundant in hops. It is found in beers and refreshment drinks. It can attenuate several factors of the metabolic syndrome. It has been reported to inhibit adipogenesis or increase cell apoptosis and therefore can be used in preventing obesity. Xanthohumol inhibited angiogenesis by suppressing NF-κB activity in pancreatic cancer. Xanthohumol may represent a novel therapeutic agent for the management of pancreatic cancer. Moreover, it is in phase I clinical trials for preventing many types of cancer. It has a range of other biological properties: antiviral, antimalarial, antibacterial and as an osteoporosis preventing agent.

Pepstatin is a pentapeptide of microbial origin. The peptide inhibits the acid proteases pepsin and cathepsin D and the pressor enzyme renin. Pepstatin was shown to provide long-lasting inhibition (3 to 6 days) of cathepsin D in vivo in non-tumor bearers particularly in spleen, liver, kidney, lung, and heart. Pepstatin may prove useful as "anticachexia" agent by decreasing proteolysis in muscle and other tissues. The in vivo pepstatin and IL-2 treatment decreased the T-cells and increased the natural killer-like LAK precursor cells, possibly also with an increase in its activity, which were further induced by in vitro IL-2 culture to generate an augmented LAK cell activity. This suggests the clinical potential of pepstatin in IL-2-related immunotherapy. In rats injected centrally with the specific cathepsin D inhibitor, pepstatin, the protease activity was inhibited up to 90% in most brain regions.