Lorbamate is a carbamate that has been studied for use as a skeletal muscle relaxer and tranquilizer. It is GABA-A receptors agonist.

Salvinorin A has been reported to be the most potent naturally occurring hallucinogen, with an effective dose in humans in the 200- to the 1,000-μg range when smoked; it has been reported to induce an intense hallucinatory experience in humans, with a typical duration of action being several minutes to an hour or so. Salvinorin A is a highly selective agonist of the kappa-opioid receptor (KOR) with few off-target effects. It is a potent and selective dilator of the cerebral vasculature, exhibits rapid penetration through the blood-brain barrier, has potent anti-inflammatory properties, and has the ability to preserve neurovascular unit integrity. As such, salvinorin A is an ideal compound for the prevention and treatment of cerebral vasospasm following subarachnoid hemorrhage.

BTZ-043 efficiently inhibits Mtb cell wall synthesis by blocking the decaprenyl- phosphoribose-2′-epimerase (DprE1), necessary for the synthesis of D-Arabinofuranose, a component of arabinogalactan and arabinomannan. Due to this mechanism it is highly selective for Mycobacteria species and does not affect the gut flora. BTZ-043 binds covalently to the enzyme and blocks it irreversibly. BTZ-043 is active against all tested Mtb strains including clinical isolated from MDR and XDR patients. The in vitro MIC ranges between ~0.1 - 80 ng/ml for fast growers, and from 1 - 30 ng/ml for members of the M. tuberculosis complex. In vivo BTZ-043 shows superior activity to INH in mouse models, most prominent after 2 months and thereafter. Synergistic effects with Rifampicin were detected in vitro as well as in vivo. In preclinical toxicology (GLP) studies, BTZ-043 showed a low toxicologic potential, it was well tolerated up to 180 mg/kg in rats. BTZ-043 showed no interaction with the CYP450 enzymes or the hERG channel. Genotoxicity and mutagenicity studies were negative. In vitro metabolism studies implicate an acceptable stability in the human organism with only one main metabolite. Protocols for GMP production in industrial scale are available and high purity of the substance can be achieved easily. Currently the final tolerability studies in two animal models are completed and studies in mice are conducted to better describe the pharmacodynamic drivers.

OC-459 is a highly potent and selective CRTH2 antagonist which is active on both the recombinant and native human receptor. The Atopix lead compound OC-459 is effective in improving lung function and symptoms in patients with atopic eosinophilic asthma. This group represents 40-50% of all asthmatics and the magnitude of improvement in the responder population is equivalent to high dose inhaled corticosteroids. OC-459 has also been shown to reduce both nasal and eye symptoms in allergic subjects exposed to grass pollen. Of particular interest is the ability of OC-459 to reduce the rate of respiratory infections, an effect related to reduction in Th2 immunity which has a damaging effect on host defence. OC-459 has also demonstrated an excellent safety profile in around 800 subjects exposed drug and no safety issues have been highlighted in long term toxicology. OC-459 is in Phase 2 clinical trial in patients with moderate to severe atopic dermatitis.

MBX-2982 is a potential first-in-class treatment for type 2 diabetes that targets G protein-coupled receptor 119 (GPR119), a receptor that interacts with bioactive lipids known to stimulate glucose-dependent insulin secretion. Preclinical data indicate that MBX-2982 is a potent selective orally-active GPR119 agonist that functions through a unique dual mechanism of action. First, it acts directly on the beta cell to increase insulin secretion. In addition, MBX-2982 stimulates release of the incretin GLP-1 from the gut. This dual action is unique and may offer improved glucose homeostasis over existing diabetes therapies, with potential for weight loss and improved islet health. MBX-2982 has completed four Phase 1 studies and one Phase 2 study. In the 4-week Phase 2 study in diabetics, MBX-2982 lowered mean weighted glucose and postprandial glucose during an extended mixed-meal tolerance test (MMTT). Treatment with MBX-2982 increased insulin, active GLP-1, and total GLP-1 during an extended MMTT. Treatment with MBX-2982 also tended to increase fasting insulin and c-peptide, and decrease fasting triglycerides. In all studies to date, MBX-2982 demonstrated dose-dependent increases in drug exposure with a profile supporting once daily oral dosing that was safe and well tolerated with no serious adverse events, adverse event trends or dose-limiting toxicities. These results provide clinical validation for the potential therapeutic benefits of MBX-2982 as a type 2 diabetes treatment.

Pefcalcitol (previously known as M518101), an analog of vitamin D3 (VD3), is an antipsoriatic drug candidate that is designed to achieve much higher pharmacological effects, such as keratinocyte differentiation. This drug is a phosphodiesterase inhibitor and is being developed as a topical ointment formulation. Pefcalcitol was involved in phase III clinical trials in the USA and in Japan in subjects with plaque psoriasis and with palmoplantar keratoderma. In addition, it participated in phase II clinical trial for the warts treatment.

MK-0812 is a potent and selective CCR2 antagonist, which was developed by Merck. This drug has entered clinical trials for both rheumatoid arthritis and multiple sclerosis. However, the rheumatoid arthritis trial was terminated because of lack of favorable outcomes when MK-0812 failed to show any early clinical improvement. The outcome of the multiple sclerosis trial of MK-0812 also had negative outcomes.

GSK-1521498 is being tested for treatment of over-eating behaviors and other control-related eating problems. This compound inhibits the effects of opioids, which are known to be involved in controlling how much we eat and the pleasure associated with eating. GSK-1521498 has also been evaluated for treatment of alcoholism, potentially promoting abstinence and preventing relapse in alcohol addiction.

Lucitanib (E-3810) is a novel multi-kinase inhibitor currently in clinical trials for its anti-angiogenic and anti-tumor activity. A Phase I/IIa clinical trial of lucitanib was initiated in 2010 and has demonstrated multiple objective responses in FGFR1 gene-amplified breast cancer patients, and objective responses were also observed in patients with tumors often sensitive to VEGFR inhibitors, such as renal cell and thyroid cancer. Lucitanib is an oral, potent inhibitor of the tyrosine kinase activity of fibroblast growth factor receptors 1 through 3 (FGFR1-3), vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3) and platelet-derived growth factor receptors alpha and beta (PDGFR alpha-beta). The most common adverse events were hypertension, asthenia, and proteinuria.

Oleandrin is a toxic cardiac glycoside found in oleander (Nerium oleander L.). Along with neandrin it is primarily responsible for the toxicity of the sap of oleander. Oleandrin has been used for many years in China and Russia for its properties as a cardiac glycoside, for both suicidal and therapeutic purposes as in treatment of cardiac insufficiency. Because of its properties as a cardiac glycoside, oleandrin interferes in some essential processes within the cell, the most important of these being the inhibition of the Na-K ATPase. This protein enables the cell to exchange the cations Na+ and K+ between the intercellular and extracellular spaces by which, for instance, electronic signaling is made possible in nerve cells. Oleandrin binds to specific amino acids in the protein, causing it to lose its function. After depolarization of the cell in which Na+ flows into the cell, the Na+ cannot be transported back into the extracellular membrane, causing the sodium gradient to disappear. This gradient is the driving force for other transport proteins, such as the sodium-calcium exchanger, which plays an important role in cardiomyocytes. To make muscle contraction possible, a calcium influx from the extracellular fluid into the cell is crucial. After the muscle contraction, the calcium is normally pumped out of the cell and exchanged for sodium. When the sodium gradient is depleted, calcium cannot be pumped back and, as a consequence, accumulates in the cardiomyocyte. As a result of the high calcium concentration, actin and myosin filaments will bind stronger, unable to relax properly to make a new contraction possible. This may result in cardiac arrhythmias, in the worst case decreasing cardiac output and causing a shortage in oxygen supply in vital tissues. Apart from being a potent toxic compound, it may also be used in therapeutic ways. Both oleandrin and oleandrigenin, as well as their relatives, may be able to inhibit proliferation of tumor cells and stimulate their apoptosis as a result of the high concentration of intracellular calcium. In addition, it inhibits excretion of fibroblast growth factor 2 through membrane interaction and through inhibition of the Na,K-ATPase pump. However, there are no results from clinical testing on humans that support any use as a cancer treatment. Oleandrin has been reported to be lethal, but exact dosages are not fully documented. The fatal blood concentration of oleandrin has been estimated for humans to be approximately 20 ng/ml in decreased blood by extrapolation of intoxication symptoms. Symptoms present in poisoned animals include bloody diarrhea and colic, the latter especially in horses. Because the leaf itself is quite bitter, only starving animals will be likely to eat the plant. The lethal dosage for animals is estimated to be about 0.5 mg/kg.