Selisistat (EX 527) was discovered by Elixir scientists as a selective human SIRT1 inhibitor and exhibits >200-fold selectivity against SIRT2 and SIRT3. Human SIRT1 is an enzyme that deacetylates the p53 tumor suppressor protein and has been suggested to modulate p53-dependent functions including DNA damage-induced cell death. It was shown that drug was highly safe in toxicology studies. Selisistat passed Phase II clinical trials to treat Huntington’s disease, but that study was discontinued.

Beloranib (also known as ZGN-433 or CKD-732), a fumagillin anticancer drug that initially was developed by CKD Pharmaceuticals for the treatment of solid tumors. Beloranib is a potent inhibitor of methionine aminopeptidase 2 (MetAP2), an enzyme that modulates the activity of key cellular processes that control metabolism. This drug was studied for the treatment of Prader-Willi syndrome and obesity caused by hypothalamic injury, including craniopharyngioma-associated obesity and severe obesity in the general population. European Commission has granted orphan drug designation for beloranib for the treatment of craniopharyngioma, a rare form of benign brain tumor and for the treatment of Prader-Willi syndrome. Beloran participated in phase III clinical trials to evaluate efficacy and safety in obese adolescent and adult subjects with Prader-Willi Syndrome, but these studies were terminated. In 2016, Zafgen, the company developed the drug, based on discussions with the regulatory authority and review of obstacles, costs and development timelines to gain marketing approval for beloranib, has decided to discontinue further development of the drug.

Linsitinib is an inhibitor of the insulin receptor and the insulin-like growth factor 1 receptor, which may result in the inhibition of tumor cell proliferation and the induction of tumor cell apoptosis. Linsitinib is in phase II clinical trials for the treatment of metastatic prostate carcinoma, gastrointestinal stromal tumors and other cancers. Common adverse events included fatigue, nausea hyperglycaemia and anorexia.

Ilepcimide, a piperine derivative, was studied in China as an anticonvulsant agent for the treatment of seizures in epilepsy children patients. However, this study was discontinued.

Picoplatin is a sterically hindered platinum (II) complex with antineoplastic properties developed for the treatment of cis-platin-resistant cancer. Picoplatin alkylates DNA, forming both inter- and intra-strand cross-linkages, resulting in inhibition of DNA replication and transcription, and the induction of apoptosis. However, in Phase III trials, picoplatin failed to meet its primary endpoint for advanced cell lung cancer. It remains in development for other cancers.

Tesofensine (also known as NS-2330) is a novel triple monoamine reuptake inhibitor with intrinsic inhibitory activity on norepinephrine (NE), serotonin (5-HT), and dopamine (DA) transporter function. It was development by NeuroSearch as a potential therapy for Alzheimer's disease (AD) and Parkinson's diseases, but these efforts have been discontinued. In phase II clinical trials with tesofensine in obese individuals, dose-related reductions in body weight, body fat and waist circumference, as well as improvements in other obesity-related endocrine factors were observed and the FDA recently endorsed the phase III trial program for this agent.

Loxoribine [RWJ 217C7] is an immunostimulant which was developed by Johnson and Johnson. It is a selective agonist for TLR7 (Toll-like receptor 7), which possesses antitumor and antiviral properties and was investigated in a rat model of endometriosis and in addition, in phase I of a clinical trial for patients with advanced cancer.

Dipraglurant (ADX48621) is a novel, potent mGluR5 negative allosteric modulator that reduced the severity of drug-induced dyskinesia in Parkinson's disease. Dipraglurant pharmacokinetic variables were similar to those of levodopa, suggesting that both drugs can be co-administered simultaneously in further studies. Dipraglurant might be useful in torsion dystonia treatment also. Detected adverse events are: sweating, dyskinesia, nausea, dizziness, and anxiety. One serious adverse event described as possible syncope.