Napabucasin (BBI608) is an orally administered small molecule that blocks stem cell activity in cancer cells by targeting the signal transducer and activator of transcription 3 pathway, which is over-activated in many types of cancer and has been shown to be an important pathway in cancer stem cell-mediated propagation of cancer. Napabucasin has already shown promising efficacy on different cancer types, both as a monotherapy and in combination with conventional chemotherapeutic agents. Early-phase trials have shown promising anti-tumor efficacy when patients are treated with napabucasin in combination with standard chemotherapy agents, and preclinical results suggest that napabucasin can synergize with chemotherapy agents, such as paclitaxel, to potentially overcome drug resistance. Encouraging phase Ib/II trial results warrant further clinical study with napabucasin and paclitaxel combination therapy, especially in malignancies where there is an urgent and unmet need for effective therapeutics, such as in patients with advanced pancreatic adenocarcinoma.

Granotapide (JTT-130) has been studied for use in treatment of diabetes mellitus type II. This intestine-specific microsomal transfer protein inhibitor has hypoglycemic effects. Granotapide is thought to block fat absorption, which results in enhanced glucose-stimulated insulin secretion and enhanced insulin sensitivity. In an animal study, granotapide improved hyperglycemia and dyslipidemia via a mechanism independent of suppression of food intake. Granotapide enhances glucagon-like peptide-1 secretion and reduces lipotoxicity. A phase 2 study has been conducted to evaluate the effect of JTT-130 on diabetes as well as the safety and tolerability of JTT-130 in obese Type 2 diabetic patients.

Bisegliptin (also known as KRP-104) was developed as an orally active dipeptidyl peptidase IV (DPPIV) inhibitor. It is known, that DPPIV inhibition reduces blood glucose through suppression of the degradation of the insulin-releasing hormone. Bisegliptin successfully completed the phase II clinical trials for patients with type 2 diabetes. However, further development of the drug has been discontinued for business reason. The company wasn’t able to find a tie-up partner to co-develop.

LAPAQUISTAT is a squalene synthase inhibitor. It was shown to lower cholesterol levels in several animal models. It was investigated for the treatment of diabetes and hypercholesterolemia, however, its development was discontinued.

Talampanel (TLP) was developed as a noncompetitive (allosteric) antagonist of the AMPA receptor. Talampanel does not act directly on the AMPA receptor, but at an allosteric site referred to as the GYKI receptor. Talampanel is being studied in the treatment of brain tumors and other brain disorders, such as epilepsy, Parkinson disease, amyotrophic lateral sclerosis, dyskinesias, glioblastoma, multiple sclerosis. It is a type of AMPA receptor antagonist. Dizziness has been the most commonly reported adverse event, with some sedation and ataxia, drowsiness and headaches reported at higher doses.

Coleneuramide (MCC-257) is a cholestane amide conjugate originated in Mitsubishi Pharma Corporation. It has been shown to enhance the effect of nerve growth factor (NGF) on cell survival and on tyrosine phosphorylation in PC12 cells. Coleneuramide is believed to act directly on TrkA receptor. In preclinical models, MCC-257 rescued clinical sign and pathological changes in rats after exposure to environmental neurotoxin methylmercury and protected against dysfunction of the peripheral nervers in hyperglycemic animals. The compound was investigated in phase 2 clinical study for the treatment of diabetic polyneuropathy, but no results were reported.

Cefetecol is a broad-spectrum cephemcarboxylate derivative with antibacterial activity patented by British pharmaceutical company Glaxo Group Ltd.

Isoindoline pazinaclone (also known as DN-2327), a partial agonist at GABAA benzodiazepine receptors, produced anxiolytic, taming and anti-convulsive effects. This neuropsychiatric drug was involved in phase II clinical trial for patients with generalized anxiety disorder. However, this study was discontinued.