Disermolide (discodermolide) is the immunosuppressant and antineoplastic agent. The marine natural product discodermolide was first isolated in 1990 from the deep-water Caribbean sponge Discodermia dissoluta. It attacks cancer cells in a similar way to the successful cancer drug Taxol that has become the best-selling anticancer drug in history. Discodermolide is a microtubule-stabilizing agent with potential for the treatment of taxol-refractory malignancies. Discodermolide is a drug that functions as an immunosuppressant and induces G2/M phase cell-cycle arrest in lymphoid and non-lymphoid cells. The cytotoxicity of discodermolide cause cell-cycle arrest by mitosis and an important alteration at the level of microtubules. Discodermolide is a potent inducer of accelerated senescence. At present, Phase I trials with discodermolide has been discontinued as a consequence of unsafe efficacy and toxicity results.

Dolastatin 10 is an unusual peptide of marine origin which binds to tubulin, inhibits microtubule assembly, resulting in the formation of tubulin aggregates and inhibition of mitosis. Dolastatin 10 has been used in trials phase II studying the treatment of Sarcoma, Leukemia, Lymphoma, Liver Cancer, among others. In case of hormone-refractory prostate cancer, it lacks significant clinical activity as a single agent and also dolastatin-10 is inactive against hepatobiliary and pancreatic carcinomas.

Tauromustine, a new taurine-based nitrosourea that was developed as an anticancer agent. Tauromustine participated in phase III clinical trial in patients with either anaplastic astrocytoma (AA) or glioblastoma (GBM) not previously treated with chemotherapy. Besides, was studied in phase III in patients with advanced colorectal cancer. Tauromustine also was used in phase II trials for the treatment of malignant glioma. However, further studies were discontinued.

Sulukast (also known as LY170680 ) is an antagonist of the cysteinyl leukotrienes C4, D4, E4 patented by Lilly Industries Ltd. for the treatment of asthma. In vitro, Sulukast was a potent, selective, and competitive antagonist of LTD4, and LTE4. It produced a concentration-dependent rightward displacement of the concentration-response curves elicited by either LTD4 or LTE4 on both the guinea-pig ileal and tracheal preparation. Intravenous Sulukast reduced in a dose-dependent manner the fall in compliance in the anesthetized guinea-pig, and the rise in total pulmonary resistance. Sulukast was also effective in reducing the increase in total pulmonary resistance to intravenous antigen in sensitized animals pretreated with mepyramine, indomethacin, and propranolol. Inhaled Sulukast was particularly effective in preventing the increase in total pulmonary resistance produced by exposure to aerosolized LTD4.

Piclonidine is imidazoline derivative. Piclonidine has a relative specificity for the hypotensive action and thus indicate that the compound differs from the chemical congener clonidine which has other pharmacological effects involving several peripheral or centrally regulated autonomic functions. Unlike clonidine, this chemically related compound did not evoke hypertensive episodes or cause sedation in animals up to the oral dose of 1 mg/kg.

Spirilene is an antipsychotic agent. In rabbit caudate nucleus (CN) spirilene exhibited Ki value of 3.5 uM at the 5-HT1R site, but produced less than 50% inhibition of [3H]5-HT binding to the 5-HT1D site even at concentrations as high as 100 uM.

Maytansine is an ansamycin antibiotic originally isolated from the Ethiopian shrub Maytenus serrata. Maytansine inhibits the assembly of microtubules by binding to tubulin at or near the vinblastine-binding site, decreases microtubule dynamic instability and cause mitotic arrest in cells. It exerts cytotoxicity against a number of tumor cell lines and inhibits tumor growth in vivo. However, in human clinical trials, maytansine showed a small therapeutic window due to its neurotoxicity and harmful effects on the gastrointestinal tract. The potent cell killing ability of maytansine can be used in a targeted delivery approach, such as an antibody-drug conjugate, for the selective delivery of the drug and destruction of cancer cells.

Metiamide is an antagonist of histamine H2-receptors synthesized at Smith Kline & French Laboratories. It potently inhibited gastric acid secretion. Metiamide demonstrated promising clinical effects in patients with duodenal ulcers but questionable safety.

PPI-2458 is a synthetic derivative of fumagillin with antineoplastic and cytotoxic properties. PPI-2458 irreversibly inhibits the enzyme methionine aminopeptidase type 2 (MetAP2), thereby preventing abnormal cell growth and angiogenesis. PPI-2458 is reported to have a better toxicity profile compared to other agents of its class. In a phase 1 clinical study, PPI-2458 was administered to patients with non-Hodgkin lymphoma. The data confirm the participation of active metabolites in the in vivo efficacy of PPI-2458. In in vitro studies, osteoclast formation and activity were inhibited by PPI-2458, a mechanism not previously attributed to MetAP-2 inhibition. PPI-2458 treatment reduced synovial and osteochondral angiogenesis, synovial inflammation, joint damage, and pain behavior. PPI-2458 exerts disease-modifying activity in experimental arthritis through its direct inhibition of several pathophysiologic processes of this disease. These results provide a rationale for assessing the potential of PPI-2458 as a novel rheumatoid arthritis therapy.

Posatirelin is a synthetic peptide that, in animal models, has been shown to improve cognitive and motor disturbances associated with aging or induced by central neurotransmission disruption. Modulation of various neurotransmission systems and activation of excitatory amino acid receptors have been suggested as possible mechanisms of action, since posatirelin increases the turnover and release of catecholamines in several brain areas as well as choline acetyltransferase activity in the cerebral cortex. In neuronal cultures, posatirelin has been shown to have trophic effects, accelerating the maturation of cerebellar granule cells and stimulating neurite growth. The benefits of posatirelin therapy in patients with late-onset Alzheimer's disease have potential clinical relevance. Significant improvements in motor, intellectual and emotional impairments were seen in posatirelin recipients. The difference in these parameters with respect to the reference and inactive drugs was significant. Posatirelin can improve cognitive and functional abilities of patients suffering from degenerative or vascular dementia. Posatirelin had been in phase III clinical trial for the treatment of cognition disorders. However, this development was discontinued.