CYT997 (Lexibulin) is a wholly synthetic compound that possesses highly potent cytotoxic activity in vitro through inhibition of microtubule polymerization. CYT997 (Lexibulin) is a potent microtubule polymerization inhibitor with IC50 of 10-100 nM in cancer cell lines. CYT997 (Lexibulin) blocks the cell cycle at the G(2)-M boundary, and Western blot analysis indicates an increase in phosphorylated Bcl-2, along with increased expression of cyclin B1. Caspase-3 activation is also observed in cells treated with CYT997 (Lexibulin) along with the generation of poly(ADP-ribose) polymerase. The compound possesses favorable pharmacokinetic properties, is orally bioavailable, and is efficacious per os in a range of in vivo cancer models, including some refractory to paclitaxel treatment. CYT997 (Lexibulin) exhibits vascular disrupting activity as measured in vitro by effects on the permeability of human umbilical vein endothelial cell monolayers, and in vivo by effects on tumor blood flow. CYT997 (Lexibulin) possesses a useful combination of pharmacologic and pharmacokinetic properties having considerable potential as a novel anticancer agent. Lexibulin was being developed by YM BioSciences as a vascular-disrupting agent (VDA) for the potential treatment of cancer, it was in phase II development on YM BioSciences ' pipeline. It appears that the development of lexibulin has been discontinued.

Terbogrel, an agent having two pharmacodynamic actions, namely inhibition of thromboxane A2 synthase and antagonism of the thromboxane A2 receptor. The antithrombotic effect of terbogrel was dose-dependent and was associated with enhanced prostacyclin production. The drug was studied for the treatment of peripheral vascular disorders, pulmonary hypertension, and thrombosis. Terbogrel participated in phase II clinical trial to investigate its safety and efficacy in patients with primary pulmonary hypertension, however, this study was discontinued due to terbogrel’s induction of leg pain.

Benzmalecene, an inhibitor of cholesterol biosynthesis, was studied for patients with hypercholesterolemia. Unfortunately, treatment was associated with undesirable side effects that prevented further using this drug in clinical.

Capeserod is benzodioxanoxadiazolone derivative patented by patented by pharmaceutical company Synthelabo S. A. as a novel 5-hydroxytryptamine4 receptor partial agonist with potent cognition-enhancing properties. In cells expressing the 5-HT4(b) and 5-HT4(e) splice variants, Capeserod acted as a partial agonist, stimulating cAMP prodn. with a maximal effect of 40 to 50% of serotonin. However, in the rat esophagus preparation, Capeserod acted as a 5-HT4 antagonist with a pKb of 8.81. In addition, Capeserod potently improved performance in several tests of learning and memory. In the object recognition task, it improved retention at 24 h when administered i.p. or p.o. (0.001-0.1 mg/kg). This effect was antagonized by the 5-HT4 antagonist SDZ 205,557, itself without effect, demonstrating that the promnesic effects of Capeserod are mediated by 5-HT4 agonism. Capeserod also reversed the cognitive deficits of aged rats in the linear maze task and the scopolamine-induced deficit of mice in the water maze task. Furthermore, the combined administration of an inactive dose of Capeserod with the cholinesterase inhibitor rivastigmine resulted in a significant promnesic effect, suggesting a synergistic interaction. Capeserod was devoid of unwanted cardiovascular, gastrointestinal, or central nervous system effects with doses up to more than 100-fold higher than those active in the cognitive tests. These results characterize Capeserod as a novel promnesic agent acting via 5-HT4 receptors, with an excellent preclinical profile.

Symetine is a benzylamine derivative patented by Eli Lilly & Co. as an antiparasitic and antispirochete agent. In preclinical models, Symetine effectively suppresses amebic liver abscess in guinea pigs.

Clorisamine is an antihistamine drug developed by Schering in the 1970s. The drug was evaluated in phase 1 clinical trial on healthy volunteers. The results show that in a therapeutic dose of 2 mg the drug did not have any effects which might lead to an impairment of driving ability.

Monometacrine is an acridan derivative and Dimethacrine metabolite patented by pharmaceutical company Siegfried A.-G. as an antidepressant.

Atropine-N-oxide hydrochloride is an alkaloid of the belladonna plants. It is the major metabolite of atropine. It is a competitive nonselective antagonist at central and peripheral muscarinic acetylcholine receptors.

Tolpadol is an analgesic agent. It is a prostaglandin synthesis inhibitor.

Denibulin is a novel antineoplastic agent. Denibulin selectively targets and reversibly binds to the colchicine-binding site on tubulin and inhibits microtubule assembly. This results in the disruption of the cytoskeleton of tumor endothelial cells, ultimately leading to cell cycle arrest, blockage of cell division and apoptosis. This causes inadequate blood flow to the tumor and eventually leads to a decrease in tumor cell proliferation. Denibulin hydrochloride had been in phase I clinical trials for the treatment of solid tumours. It was generally well tolerated and showed decrease in tumor vascular parameters. However, no recent development has been reported.