Sparsomycin is a model protein synthesis inhibitor that blocks peptide bond formation by binding to the large ribosome subunit. It is a unique dipeptidyl alcohol, consisting of a uracil acrylic acid moiety and a monooxo-dithioacetal group. Sparsomycin is a cytotoxic drug exhibiting a broad spectrum of in vitro activity against murine tumors and many tumor cell lines. It also appears to be a potent stimulator of the antitumor activity of cisplatin against L1210 leukemia in vivo. However, because of its toxicity, the antitumor activity of sparsomycin on murine tumors in vivo has been disappointing. Sparsomycin has shown cytostatic activity in a number of in vivo tumor systems, therefore, it was introduced in 1964 in a clinical Phase I study. Two of the five patients of this study developed an ocular toxicity, probably caused by sparsomycin, and so this Phase I study was stopped prematurely.

Sabcomeline (SB-202026) is a potent and functionally selective M1 receptor partial agonist that originally was developed by GlaxoSmithKline. Sabcomeline had been in phase III clinical trials for the treatment of Alzheimer's disease and phase II for schizophrenia and major depressive disorder. In addition, it was studied for patients with Type 2 diabetes mellitus. However, due to poor results, the development of this drug was discontinued.

Ezlopitant (CJ-11974) is a non-peptide neurokinin-1 receptor antagonist. Pfizer was developing ezlopitant for the potential treatment of irritable bowel syndrome and chemotherapy-induced emesis. Development of ezlopitant has been discontinued.

LAPAQUISTAT is a squalene synthase inhibitor. It was shown to lower cholesterol levels in several animal models. It was investigated for the treatment of diabetes and hypercholesterolemia, however, its development was discontinued.

Sulfatroxazole is a sulfamide derivative patented by Swiss multinational healthcare company F. Hoffmann-La Roche & Co., A.-G. as an antibacterial agent and bacteriostatic antibiotic. Sulfatroxazole competitively inhibits dihydropteroate synthase preventing the formation of dihydropteroic acid, a precursor of folic acid which is required for bacterial growth. Sulfatroxazole is a component present in various veterinary drugs.

Neosaxitoxin is a site-1 specific sodium channel blocker which acts synergistically with local anesthetics to provide surgical anesthesia by peripheral nerve blocks or local infiltration and markedly increases the duration of post-operative analgesia. Saxitoxin and neosaxitoxin, small molecules synthesized by marine dinoflagellates and freshwater cyanobacteria. Neosaxitoxin, one of the saxitoxin analogs, differs from saxitoxin by the addition of one oxygen atom, wherein the hydrogen (-H) at Nitrogen 1 in saxitoxin is replaced by a hydroxyl group (-OH) in neosaxitoxin. Neosaxitoxin has shown greater potency than saxitoxin and its analogs and is also more potent than tetrodotoxin in in vitro and in vivo animal studies.Neosaxitoxin showed an effective local anesthetic effect when injected in the subcutaneous plane. The efficacy of a 50-ug dose of neosaxitoxin was shown. Neosaxitoxin has poor affinity for the cardiac isoform of the sodium channel and does not cross the blood–brain barrier, thus this compound is virtually devoid of cardiac and central nervous system toxicity—the limiting toxicities of traditional local anesthetics.

Dexniguldipine (B8509-035, (-)-(R)-niguldipine) is a new dihydropyridine derivative, that exerts selective antiproliferative activity in a variety of tumor models and, in addition, has a high potency in overcoming multidrug resistance. Dexniguldipine is ( - )-(R)-enantiomer of niguldipine, of which the ( )-(S)-enantiomer shows pronounced cardiovascular hypotensive activity due to its high affinity for the voltage-dependent Ca2 channel. As compared with the (S)-enantiomer, the (R)-enantiomer has a 40-fold lower affinity for the Ca 2 channel and, accordingly, only minimal hypotensive activity in animal pharmacology models. Dexniguldipine have shown antiproliferative activity in several tumor cell lines, but the concentrations necessary to inhibit growth have varied by several orders of magnitude between cell lines. Initial results of preclinical investigations for the evaluation of the mechanism of its antiproliferative activity demonstrate that dexniguldipine interferes with intracellular signal transduction by affecting phosphoinositol pathways, protein kinase C expression, and intracellular Ca 2 metabolism. In a series of human tumor xenografts in vitro, dexniguldipine demonstrated selective antiproliferative activity against several tumor types, e.g., melanoma and renal-cell carcinoma. Striking results were obtained in a hamster model, in which neuroendocrine lung tumors could be completely eradicated by 20 weeks of oral treatment with 32.5mg/kg dexniguldipine, whereas Clara-cell-type lung tumors were not affected. In in vitro studies, dexniguldipine has been found to bind to P-glycoprotein (P-gp) and to enhance the cytotoxicity of chemotherapeutic agents such as doxorubicin and etoposide in several cell lines The synergistic effect may well be associated with the reversal of multidrug resistance (MDR) related to the activity of P-gp. In the clinical therapy of cancer, resistance to many cytostatic drugs is a major cause of treatment failure. However, the high potency of dexniguldipine (about 10-fold as compared with that of verapamil in vitro) and its low cardiovascular activity provide the opportunity to achieve blood or tumor concentrations that might be high enough to overcome Mdr 1 resistance in patients without producing dose-limiting cardiovascular effects.

Encaleret (JTT-305 or MK-5442) is a potent oral short-acting calcium-sensing receptor (CaSR) antagonist and transiently stimulates endogenous parathyroid hormone (PTH) secretion. CaSR antagonists stimulate endogenous PTH secretion through CaSR on the surface of parathyroid cells and thereby may be anabolic agents for osteoporosis. Japan Tobacco and Merck were developing encaleret for the treatment of osteoporosis however development has been discontinued.