Mavoglurant (AFQ056) was developed as a new metabotropic glutamate receptor 5 (mGluR5) antagonist. The efficacy of mavoglurant in humans has been assessed in L-dopa induced dyskinesia in Parkinson's disease and Fragile X syndrome in proof of principle clinical studies. However, Novartis had announced that the company would be discontinuing its development program in Fragile X following negative results in a large international clinical trial in adults, and more recently in a trial in adolescents. In both placebo-controlled trials, patients taking mavoglurant did not show improvement over placebo in any outcome measures. In patients with L-Dopa-induced dyskinesias studies failed to meet the primary objective of demonstrating improvement of dyskinesia. Mavoglurant was also investigated in phase II clinical trials to reduce chorea in Huntington's disease, but the target result was not achieved. Currently Novartis is conducting a phase II clinical trial to demonstrate whether or not this drug can benificially reduce cocaine use in Cocaine Use Disorder.

Omtriptolide (previously known as PG490-88 or F60008), an immunosuppressant that has been shown to be the safe and potent antitumor agent and it has been approved entry into Phase I clinical trial for the treatment of prostate cancer in the USA. In addition, the drug is participating in phase I clinical trial for the treatment of myeloid leukemia. Experiments on animals have shown omtriptolide was highly effective in the prevention of murine graft-versus-host disease (GVHD). The immunosuppressive effect of the drug was mediated by inhibition of alloreactive T cell expansion through interleukin-2 production. However, this study was discontinued. Recently published article has shown omtriptolide possesses the potential as a prophylactic agent to prevent ischemia/reperfusion (I/R)-induced lung injury.

Veribulin is a novel microtubule destabilizer that both functions as a potent cytotoxin and acts as a vascular disrupting agent (VDA). It binds to the same (or nearby) sites on β-tubulin as colchicine. It is capable of evading multidrug resistance pumps and, thus, achieves high CNS concentrations. It is efficacious in multiple xenograft models without CNS toxicity. Veribulin had previously demonstrated pre-clinical and clinical activity in multiple tumor types. Veribulin is in phase II clinical trial for the treatment of Glioblastoma and Malignant melanoma.

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.

Perzinfotel (EAA-090) is a novel squaric acid amide derivative that has been identified as a potential treatment for ischemic brain damage resulting from stroke. EAA-090 is a competitive inhibitor at the NMDA-selective subtype of the glutamate receptor. The compound demonstrates potent inhibitory activity in both in vitro and in vivo models of NMDA-induced excitotoxicity and provides neuroprotective efficacy in several animal models of stroke. EAA-090 is unique among competitive NMDA antagonists in displaying a clear separation between predicted efficacious dose and doses that induce PCP-like psychotomimetic side effects in both animals and humans. This unique profile makes EAA-090 an exciting candidate for assessing the neuroprotective potential of the competitive NMDA mechanism.

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.

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.[

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.