Cevipabulin is a synthetic, water-soluble tubulin-binding agent with potential antineoplastic activity. Cevipabulin appears to bind at the vinca-binding site on tubulin but seems to act more similar to taxane-site binding agents in that it enhances tubulin polymerization and does not induce tubulin depolymerization. The disruption in microtubule dynamics may eventually inhibit cell division and reduce cellular growth.

A second generation of HDACs, synthetic benzamide-containing HDACs such as Tacedinaline (CI-994), have reached phase I and II clinical trials. It has been investigated for its applications to the treatment of cancers such as Breast cancer and Colorectal cancer. Tacedinaline has been in phase III clinical trials by Pfizer for the treatment of advanced non-small cell lung cancer and pancreatic cancer combined with gemcitabine. However, this research has been discontinued. Mechanism of Action: Angiogenesis inhibitors; Histone deacetylase inhibitors. Pharmacokinetics showed that CI-994 absorption and disposition were unaffected by carboplatin and paclitaxel coadministration.

Atrasentan (ABT-627, A-127722) is a selective endothelin A receptor antagonist. Atrasentan is being developed by AbbVie as an oral treatment for diabetic nephropathies.Abbott Laboratories was conducting clinical development of atrasentan for the treatment of certain cancers, including phase II trials for prostate cancer. However, no recent development has been reported for cancer indications and development is presumed to be discontinued.

Tetrodotoxin (TTX) is a potent marine neurotoxin that blocks voltage-gated sodium channels (VGSCs). VGSCs play a critical role in neuronal function under both physiological and pathological conditions. TTX has been extensively used to functionally characterize VGSCs, which can be classified as TTX-sensitive or TTX-resistant channels according to their sensitivity to this toxin. Wex Pharmaceuticals is investigating tetrodotoxin for the treatment of chronic and breakthrough pain. The toxin is currently undergoing Phase III clinical trials in Canada as a systemic analgesic for inadequately controlled pain due to advanced cancer, especially where the pain has neuropathic features. In addition, TTX is in Phase II clinical trials to study its ability in moderate to severe neuropathic pain caused by chemotherapy.

Licofelone (ML 3000) is a pyrrolizine derivative originally discovered by Merckle GmbH and developed by EuroAllaince with a unique pharmacological profile, which comprises optimal gastrointestinal tolerability and high analgesic and anti-inflammatory activity. These effects are due to balanced and selective inhibition of both cyclo-oxygenase and 5-lipoxygenase. Inhibition of 5-lipoxygenase may reduce the gastrointestinal toxicity associated with other non steroidal anti-inflammatory drugs, which only inhibit cyclooxygenase. Licofelone also has antipyretic and antiaggregatory properties. Clinical and preclinical trials were also undertaken for osteoarthritis, rheumatoid arthritis, asthma, pain and inflammation. However, development for these indications appear to have been discontinued.

Kynurenic acid is a product of the normal metabolism of amino acid L-tryptophan which has been shown to have a neuroactive profile. It exhibits activity against NMDA receptors and Neuronal acetylcholine receptor subunit alpha-7. It has been investigated as a potential therapeutic compound and as a biomarker in a number of neurological disorders. Although Kenyruic acid exhibits a poor penetration of the blood-brain barrier, it remains to be of particular interest to those researching Schizophrenia.

Rubitecan [Orathecin™] is a topoisomerase I inhibitor extracted from the bark and leaves of the Camptotheca acuminata tree, which is native to China. Rubitecan is an oral compound being developed for the treatment of pancreatic cancer and other solid tumours by SuperGen. Rubitecan binds to and inhibits the enzyme topoisomerase I and induces protein-linked DNA single-strand breaks, thereby blocking DNA and RNA synthesis in dividing cells; this agent also prevents repair of reversible single-strand DNA breaks.

Tyramine is a naturally occurring monoamine compound and trace amine derived from the amino acid tyrosine. Tyramine occurs widely in plants and animals, and is metabolized by the enzyme monoamine oxidase. Tyramine is an alpha-adrenergic agonist. Hypertension can occur, from ingestion of tyramine-rich foods in conjunction with monoamine oxidase inhibitors. The possibility that tyramine acts directly as a neurotransmitter was revealed by the discovery of a G protein-coupled receptor with high affinity for tyramine, called TAAR. It exhibits sympathomimetic effects by causing the release of endogenic norepinephrine. It has been used in mydriatic eyedrops. This has been said to reduce the intraocular pressure in rabbits and in some patients with open-angle glaucoma.

2-Nitro-p-phenylenediamine is a low molecular weight red dye which is able to penetrate into hair shafts; this compound is one of the most commonly used dyes in semi-permanent hair colorants. 2-Nitro-p-phenylenediamine is also an ingredient in permanent hair dye formulations.

K-252a, a metabolite isolated from the culture broth of Nocardiopsis sp. K-252a, was found to exhibit an extremely potent inhibitory activity on protein kinase C. The IC50 value was 32.9 nM. K252a is a potent inhibitor of various protein kinases including Protein kinase A, Protein kinase C and Protein kinase G. It acts by competition with the ATP binding site with Ki values of 18-25 nM. K252a also acts as a specific and potent inhibitor (IC50 = 3 nM) of Trk receptors and thus selectively blocks the effects of nerve growth factor (NGF) on PC12 cells. At lower concentrations, K252a can act as a neuroprotective compound, promoting survival of primary neuronal cultures. This alkaloid induces apoptosis and cell cycle arrest by inhibiting Cdc2 and Cdc25.4 Recently, K252a was found to improve psoriasis in a SCID mouse-human skin model and to suppress referred mechanical hypersensitivity and neuropeptide up-regulation associated with acute pancreatitis.