Volixibat (SHP626; formerly LUM002) is a potent inhibitor of the apical sodium-dependent bile acid transporter (ASBT) that was developed for the treatment of nonalcoholic steatohepatitis. Volixibat participated in phase II clinical trial to investigate its safety, effectiveness in adults with nonalcoholic steatohepatitis. However, this study was discontinued, without any further explanation for the possible causes. In addition, volixibat was studied in a clinical trial in healthy adults and in patients with type 2 diabetes mellitus, where was shown that the drug was generally well tolerated.

Pterostilbene is a naturally derived compound found primarily in blueberries and Pterocarpus marsupium heartwood. The multiple benefits of pterostilbene in the treatment and prevention of human disease have been attributed to its antioxidant, anti-inflammatory, and anti-carcinogenic properties leading to improved function of normal cells and inhibition of malignant cells. The antioxidant activity of pterostilbene has been implicated in anti-carcinogenesis, modulation of neurological disease, anti-inflammation, attenuation of vascular disease, and amelioration of diabetes. Pterostilbene increases LDL and reduces blood pressure in adults. Low doses of pterostilbene seem to hold some benefit for cognition.

Recilisib (also known as EX-RAD or ON-01210) is a radioprotectant, which means that this compound can protect cells from harmful effects of ionizing radiation. Unlike other radioprotectors, recilisib is not a free-radical scavenger or responsible for cell cycle arrest. Recilisib was suggested to have a different radiation protection mechanism involving DNA repair pathways. This compound has been studied as prophylactic (use prior to radiation exposure) and therapeutic (after exposure to radiation) drug. In studies with healthy volunteers, recilisib was rapidly absorbed and well-tolerated, with only mild adverse events. Phase I clinical trials have been completed.

Sarizotan (also known as EMD-128,130), a chromane derivative that was developed as a selective 5-HT1A receptor agonist and D2 receptor antagonist. Experiments on animal models have shown that the drug effectively suppressed levodopa-induced dyskinesia in primate and rodent models of Parkinson's disease, and tardive dyskinesia in a rodent model. Sarizotan participated in phase II/III clinical trials in the treatment of dyskinesia associated with the dopaminergic treatment of Parkinson's disease. However, further development for this disease was discontinued by Merk, because phase III did not confirm earlier Phase II findings. On July 14, 2015, Newron Pharmaceuticals, research, and development company focused on the novel central nervous system (CNS) and pain therapies, announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to sarizotan for treatment of Rett syndrome. Besides, the drug now is an ongoing clinical trial phase II/III to investigate its the tolerability and efficacy in reducing respiratory abnormalities in Rett Syndrome.

Cipralisant (GT-2331) is an H3-receptor ligand developed by Gliatech in the late 1990s. The drug exhibits complex pharmacology: it behaves as an antagonist in a guinea pig jejunum contraction assay and mouse disogenia model, as a partial agonist in a rat brain synaptosome model, and as a full agonist at recombinant H3 receptors. In preclinical models, cipralisant enhanced wakefulness and improved learning in developmental rat models. In 2000 cipralisant was investigated in the clinical trials for the treatment of attention-deficit hyperactivity disorder, but due to the bankruptcy of Gliatech the development of the drug was discontinued.

Bicifadine (DOV-220075) is not a narcotic and is well-tolerated and, in preclinical studies, has been shown not to act at any opiate receptor, but inhibits monoamine neurotransmitter uptake by recombinant human transporters in vitro with a relative potency of norepinephrine:serotonin:dopamine of 1:2:17. Bicifadine was in Phase II clinical trial for pain caused by diabetic neuropathy, in addition, was in phase III clinical trial to treat Chronic Low Back Pain, but that studies were discontinued

Zonampanel (also known as YM872) was developed as selective, potent and highly water-soluble competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist. Zonampanel possesses the neuroprotective effect against focal cerebral ischemia and participated in phase II clinical trials in acute stroke patients. However, because of the severe effects, including hallucinations, agitation, and catatonia the further studied were terminated.

Swainsonine is an indolizidine alkaloid found in Australian Swainsona canescens, North American plants of the genera Astragalus and Oxytropis and also in the fungus Rhizoctonia leguminocola. It is competitive inhibitor of Golgi alpha-mannosidase II and lysosomal alpha-mannosidases. This compound has been reported to be a potent antiproliferative and immunomodulatory agent. However, no evidence of anti-tumor activity of swainsonine was seen in phase II clinical trial, in patients with locally advanced or metastatic renal cell carcinoma. Adverse events such as fatigue, nausea and diarrhea were common but generally mild. Swainsonine is locoweed toxin. Locoweed poisoning is seen throughout the world and annually costs the livestock industry millions of dollars. Swainsonine inhibits lysosomal alpha-mannosidase and Golgi mannosidase II. Poisoned animals are lethargic, anorexic, emaciated, and have neurologic signs that range from subtle apprehension to seizures.

Mangafodipir (sold under the brand name Teslascan as mangafodipir trisodium) is a contrast agent delivered intravenously to enhance contrast in magnetic resonance imaging (MRI) of the liver. Mangafodipir is a manganese (Mn2+) chelate with the ligand fodipir (dipyridoxyl diphosphate or DPDP). Mangafodipir trisodium is metabolised (dephosphorylated) and partially transmetallated (manganese exchanged for zinc) after intravenous administration. Manganese that is released from mangafodipir is taken up by hepatocytes thereby increasing the SI of normal liver tissue. This may result in an improvement of the detection of liver metastases, which usually have no hepatocytes. The metabolites of fodipir are renally excreted, whilst the biliary route mainly excretes manganese. Mangafodipir was withdrawn from the US market in 2003 and the European market in 2012.

Amifostine is an organic thiophosphate cytoprotective agent known chemically as 2-[(3¬ aminopropyl)amino]ethanethiol dihydrogen phosphate (ester), it’s adjuvant used in cancer chemotherapy and radiotherapy involving DNA-binding chemotherapeutic agents. It is marketed under the trade name Ethyol. Amifostine is a prodrug and is dephosphorylated by alkaline phosphatase in tissues to a pharmacologically active free thiol metabolite. This metabolite is believed to be responsible for the reduction of the cumulative renal toxicity of cisplatin and for the reduction of the toxic effects of radiation on normal oral tissues. The ability of Ethyol to differentially protect normal tissues is attributed to the higher capillary alkaline phosphatase activity, higher pH and better vascularity of normal tissues relative to tumor tissue, which results in a more rapid generation of the active thiol metabolite as well as a higher rate constant for uptake into cells. The higher concentration of the thiol metabolite in normal tissues is available to bind to, and thereby detoxify, reactive metabolites of cisplatin. This thiol metabolite can also scavenge reactive oxygen species generated by exposure to either cisplatin or radiation. Healthy cells are preferentially protected because amifostine and metabolites are present in healthy cells at 100-fold greater concentrations than in tumor cells.