Patupilone is a compound isolated from the myxobacterium Sorangium cellulosum. Similar to paclitaxel, Patupilone induces microtubule polymerization and stabilizes microtubules against depolymerization conditions. In addition to promoting tubulin polymerization and stabilization of microtubules, this agent is cytotoxic for cells overexpressing P-glycoprotein, a characteristic that distinguishes it from the taxanes. Epothilone B may cause complete cell-cycle arrest. Patupilone failed a phase III trial for ovarian cancer in 2010.

Bitopertin is a Glycine transporter type 1 inhibitor which was developed by Hoffmann-La Roche for the treatment of patients with schizophrenia. The drug was shown to be potent in vitro, however it failed to meet primary endpoints in phase III. Bitopertin was also tested for the treatment of obsessive-compulsive disorder, but the development stopped in phase II.

Isoquercetin is a flavonoid, derivative of quercetin. It was isolated from various plant species including Ammothamnus Lehmanii, Caragana alaica, Cicer baldshuanicum, C. macroconthum, C. pungens, Euphorbia cyparissias, E. helioscapia, E. lathyris, E. lucida, E. purporata and others. It demonstrated radical scavenging activity, inhibitory effects on Na+/K+-ATPase and positive inotropic activity. It is protein disulfide isomerase (PDI) inhibitor. As a PDI inhibitor, this agent blocks PDI-mediated platelet activation, and fibrin generation, which prevents thrombus formation after vascular injury. Isoquercetin inhibited the replication of both influenza A and B viruses at the lowest effective concentration. Isoquercetin activates the ERK1/2-Nrf2 pathway and protects against cerebral ischemia-reperfusion injury in vivo and in vitro. It is being investigated for prevention of thromboembolism in selected cancer patients and as an anti-fatigue agent in kidney cancer patients treated with sunitinib.

Tozadenant (SYN115) is an adenosine A2A receptor antagonist initially developed for treatment of Parkinson's disease but may also have utility in other CNS disorders. A2a receptors are expressed in high concentration in the striatum of the brain and play an important role in regulating motor function. Tozadenant blocks the effect of endogenous adenosine at the A2a receptors, resulting in the potentiation of the effect of dopamine at the D2 receptor and inhibition of the effect of glutamate at the mGluR5 receptor. This enables restoration of motor function in Parkinson’s disease. Tozadenant has the potential for use as mono-therapy or adjunctive therapy in combination with L-Dopa and dopamine agonists for the treatment of the motor and non-motor symptoms associated with Parkinson’s disease. may also have neuroprotective effects, which raises the possibility that it could slow the deterioration of dopamine producing cells and modify disease progression. As was reported in international, multicentre, phase 2b, randomised, double-blind, placebo-controlled, parallel-group, dose-finding clinical trial of tozadenant in levodopa-treated patients with Parkinson's disease who had motor fluctuations tozadenant at 120 or 180 mg twice daily was generally well tolerated and was effective at reducing off-time.

LY404039 [(-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]-hexane-4,6-dicarboxylic acid] is an agonist of orthosteric metabotropic glutamate receptor (mGluR)2/3. In addition, it acts as an agonist at dopamine D2 receptors. LY404039 demonstrated broad antipsychotic and anxiolytic efficacy across multiple animal models. LY-2140023 is a methionine amide prodrug of LY-404039 being developed by Eli Lilly & Co for the potential oral treatment of schizophrenia.

Cebranopadol is a novel analgesic nociceptin/orphanin FQ peptide (NOP) and opioid receptor agonist. Cebranopadol, by its combination of agonism at NOP and opioid receptors, affords highly potent and efficacious analgesia in various pain models with a favorable side effect profile. Cebranopadol displays analgesic, antiallodynic and antihyperalgesic properties in several rat models of acute nociceptive, inflammatory, cancer and neuropathic pain. Unlike morphine, cebranopadol did not disrupt motor coordination and respiration at doses within and exceeding the analgesic dose range possessing a broader therapeutic window than classical opioids. It is currently in clinical development for the treatment of severe chronic nociceptive and neuropathic pain.

Intepirdine, also known as SB-742457, RVT-101, was originally developed by GlaxoSmithKline (GSK) as an antagonist of the serotonin receptor 6 (5-HT6). GSK sold the rights for further study of this drug to Axovant Sciences in 2014. Intepirdine is in phase 3 clinical trial for Alzheimer's and in a phase 2 trial for dementia with Lewy bodies.

Trigonellamide (1-Methylnicotinamide) is a metabolite of nicotinamide and is produced primarily in the liver by nicotinamide N-methyltransferase. Trigonellamide may be an endogenous activator of prostacyclin (PGI2) production and thus may regulate thrombotic as well as inflammatory processes in the cardiovascular system. The mechanisms of action of Trigonellamide involve the activation of PGI2 release driven by cyclooxygenase 2 (COX-2). PGI2 releasing capacity of 1- Trigonellamide was shown to afford not only anti-thrombotic but also fibrinolytic, anti-inflammatory and gastroprotective effects. Interestingly, Trigonellamide did not directly either affect the activity of leucocytes or release PGI2 in the perfused rat hindquarters model. Still, Trigonellamide, due to its PGI2 releasing capacity, might serve as a hepatoprotective agent that protects against Concanavalin-A induced liver injury through the downregulation of interleukin-4 (IL-4) and tumor necrosis factor-α signalization (TNF-α). In addition to its anti-platelet, anti-thrombotic and anti-inflammatory activities, 1-MNA has also been shown to restore endothelial function in diabetic hyperglycemic rats, as well as to improve endothelial function in humans. PGI2 displays anti-metastatic activity, and the PGI2 releasing activity of Trigonellamide, the potential application of exogenous Trigonellamide to prevent metastatic cancer.

Tasisulam sodium, previously known as LY573636, were initially recognized by Eli Lilly for their significant antiproliferative activities in solid tumor cell lines, but their mechanism of action was unknown. Subsequent studies have revealed that LY573636 induces apoptosis via a mitochondrial-mediated mechanism that appears unique among other anti-cancer compounds. This drug was in the phase III clinical trial for the treatment of Metastatic Melanoma and in phase II for the treatment Non-Small-Cell Lung Cancer, breast cancer, ovarian cancer, but these studies were discontinued. In vivo pharmacokinetic studies in rats and dogs indicate that tasisulam is metabolized primarily by the liver, and has low total plasma clearance with a relatively long half-life. In addition, there was preclinical evidence of a correlation between the maximum plasma concentration (Cmax) of tasisulam and toxicity.

Igmesine is a sigma-1 receptor agonist. It was assayed in clinical trials targeting major depressive disorder. Igmesine is the only antisecretory agent that we have tested to date that inhibits both cholera toxin and the E. coli enterotoxins. Sigma receptors are known to be present on nerves in the enteric nervous system and this would seem to be a potentially useful class of drugs to pursue for the treatment of secretory diarrhoea in humans. It was shown that when Alzheimer's disease rats were submitted to the conditioned fear stress test, igmesine can significantly reduce the stress-induced motor suppression, indicating exogenous σ-1 receptor agonists may alleviate Alzheimer's disease-associated depressive symptoms.