Basimglurant is a potent, selective, and safe mGlu5 inhibitor with good oral bioavailability and long half-life supportive of once-daily administration, good brain penetration, and high in vivo potency. It has antidepressant properties that are corroborated by its functional magnetic imaging profile as well as anxiolytic-like and antinociceptive features. In electroencephalography recordings, basimglurant shows wake-promoting effects followed by increased delta power during subsequent non-rapid eye movement sleep. Basimglurant has favorable drug-like properties, a differentiated molecular mechanism of action, and antidepressant-like features that suggest the possibility of also addressing important comorbidities of MDD including anxiety and pain as well as daytime sleepiness and apathy or lethargy. Basimglurant is being under development by Roche for the treatment of treatment-resistant depression (as an adjunct). It is in phase II clinical trials for this indication.

Daniquidone, also known as Batracylin, is a water-insoluble heterocyclic amide with potential antineoplastic activity. Daniquidone inhibits topoisomerases I and II, thereby inhibiting DNA replication and repair, and RNA and protein synthesis. Batracylin advanced as an anticancer agent to Phase I clinical trials where dose limiting hemorrhagic cystitis (bladder inflammation and bleeding) was observed.

Nemorubicin, a doxorubicin derivative, is a DNA-intercalator, topoisomerase and RNA synthesis inhibitor that was undergoing development with Nerviano Medical Sciences (Nerviano MS; formerly Pharmacia Italia) for the treatment of solid tumours, specifically, the loco-regional treatment of primary liver tumours (hepatocellular carcinoma). The drug is active on tumors resistant to alkylating agents, topoisomerase II inhibitors and platinum derivatives. It works primarily through topoisomerase I inhibition. Of note, Nemorubicin is active in cells with upregulation of the nucleotide excision repair (NER) pathway, where current therapies fail. Nemorubicin is biotransformed in the liver into cytotoxic metabolites that may further contribute to render this drug highly active against primary liver tumors or liver metastases. Clinical trials were conducted in Europe, US and China with Nemorubicin given at different dose-schedules and by different routes of administration: as single agent by systemic IV route, oral route and by intra-hepatic artery (IHA) infusion alone or in combination with cisplatin.

Tecalcet (also known as KRN-568; NPS-R-568; R-568), is an oral calcium channel agonist potentially for the treatment of hyperparathyroidism. Calcimimetics, such as Tecalcet, are agonists and activate the calcium channel in a non-competitive fashion. Tecalcet does not compete directly with calcium that activates the receptor through binding in the extracellular domain of these receptors, but rather, calcimimetics such as Tecalcet, bind allosterically in the seven transmembranes to ‘sensitize’ the receptor to extracellular calcium. Tecalcet acts as an agonist of the calcium receptors of the parathyroid cells, causing a decrease in PTH release. Tecalcet also acts on the parafollicular cells (C-cells) of the thyroid gland, resulting in an increase in calcitonin release. These effects ultimately lead to a decrease in plasma calcium concentrations. Studies in rats have shown that oral administration of R-568 at doses ranging from 3 to 100 mg/kg caused a rapid (<30 minutes) decrease in plasma PTH concentrations and an increase in calcitonin concentrations, accompanied by a dose-dependent decrease in calcium concentrations. Tecalcet had been in phase II clinical trials by for the treatment of hyperparathyroidism, postmenopausal osteoporosis and rheumatic disorders in Japan and US. Development of Tecalcet has been discontinued.

CPI-613 is a lipoate derivative synthesized to be catalytically inert but to potentially mimic lipoate catalytic intermediates. The drug is in phase II of clinical trials for the treatment of Myelodysplastic syndromes; Pancreatic cancer; Small cell lung cancer; Solid tumors; Bile duct cancer; Acute Myeloid leukemia. The mechanism of CPI-613 action can be explained by (I) inhibition of tumor cell pyruvate dehydrogenase complex (PDC) through activation of pyruvate dehydrogenase kinases leading to inactivating phosphorylation of the E1alpha-subunit of PDC; and (II) inhibition of alpha-ketoglutarate dehydrogenase.

Eniporide belongs to the new class of drugs that specifically inhibit the Sodium/hydrogen exchanger 1 (NHE-1) isoform, which is the predominant isoform in the cardiac myocytes. Extensive preclinical studies, in vitro and in animals, have suggested that NHE inhibition with eniporide before the onset of ischemia is a very effective and reproducible means of limiting the extent of infarction and that this agent provides protective benefit even when given just before reperfusion. Eniporide had been in phase II clinical trial for the treatment of myocardial infarction. Administration of the eniporide, before reperfusion therapy in patients with acute ST-elevation myocardial infarction, did not limit infarct size or improve clinical outcome.

Brivanib is a pyrrolotriazine-based compound and an inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) with potential antineoplastic activity. It specifically targets and strongly binds to human VEGFR-2, a tyrosine kinase receptor and pro-angiogenic growth factor expressed almost exclusively on vascular endothelial cells. Blockade of VEGFR-2 by this agent may lead to an inhibition of VEGF-stimulated endothelial cell migration and proliferation, thereby inhibiting tumor angiogenesis. Brivanib has a moderate potency compared to VEGFR-2 against VEGFR-1 and FGFR-1 as well. Brivanib is suggested to be efficient in treatment of hepatocellular carcinoma (HCC). As first-line and as second-line therapy brivanib demonstrated promising antitumor activity and a manageable safety profile in patients with advanced, unresectable HCC in phase II clinical trials. On 3 march 2011, orphan designation was granted by the European Commission to Bristol-Myers Squibb for brivanib alaninate for the treatment of hepatocellular carcinoma.[

Edaglitazone have a clear PPAR-gamma agonist profile, with predominant PPAR-gamma activity and little PPAR-alpha activity. Edaglitazone was reported to significantly improve insulin sensitivity and enhance the rate of glucose oxidation in both the presence and absence of insulin. Additional studies have shown that edaglitazone affects muscle glucose metabolism by additional mechanisms other than PPAR-gamma activation. Phase I clinical studies have revealed that edaglitazone is well-tolerated and capable of significantly improving glucose homeostasis. Edaglitazone had been in phase II clinical trials for the treatment if type 2 diabetes. However, this research has been discontinued.

Torcetrapib is a CETP inhibitor which was developed by Pfizer for the treatment of diseases associated with elevated level of cholesterol. The drug was tested in phase III (in combination with atorvastatin) of clinical trials in coronary heart disease patients as well as in patients with hyperlipoproteinemia, hypertriglyceridemia, hypercholesterolemia, hyperlipidemia, however its development was terminated due to the high risk of death and heart problems.

Triapine (3-aminopyridine-2-carboxaldehyde thiosemcirbazone, (3-AP; NTO-1151; OCX-0191) is a novel small molecule ribonucleotide reductase inhibitor that acts on the M2 (R2) subunit. Ribonucleotide reductase is an enzyme involved in the de novo synthesis of deoxyribonucleotides, which are critical for DNA replication and DNA repair. Triapine has been used in trials phase II studying the treatment of Lung Cancer, Kidney Cancer, Prostate Cancer Pancreatic Cancer, among others. Recently was published the article describing, that the triple combination triapine-cisplatin-paclitaxel was safe and provided a rational basis for a follow-up phase II trial to evaluate the efficacy and progression-free survival in women with metastatic or recurrent uterine cervix cancer.