1-(2-DEOXY-2-FLUORO-β-D-ARABINOFURANOSYL)URACIL (FAU) is a thymidine analog. In several cancer cell lines, FAU was phosphorylated intracellularly to its monophosphate, 1-(2-deoxy-2-fluoro--Darabinofuranosyl) uracil monophosphate (FAUMP), by thymidine kinase and methylated in the 5-position by thymidylate synthase to form the product, 1-(2-deoxy-2-fluoro- -D-arabinofuranosyl) 5-methyluracil monophosphate (FMAUMP). FAU strongly inhibits the growth of tumor cells with high thymidylate synthase activity. FAU had been in phase I clinical trial for the treatment of advanced solid tumors.

LAVOLTIDINE, also known as loxtidine, is a highly potent and selective histamine H2-receptor antagonist. It is a member of triazoles. It produces gastric carcinoid tumors in rodents that is why its clinical development was discontinued.

Balicatib is a potent cathepsine K inhibitor that was developed for the treatment of knee osteoarthritis. The development of Balicatib was terminated in phase II due to the occurrence of skin rashes and rarer incidences of morphea-like skin changes.

There is no much available information related to the biological and pharmacological application of imidoline, but this compound has been found to be as potent as chlorpromazine in increasing striatal DOPA accumulation and prolactin secretion in vivo. Imidoline exhibited only weak inhibitory activity towards dopamine-sensitive adenylate cyclase and 3H-spiroperidol binding to striatal membranes in vitro. A proposed active conformation involves intramolecular hydrogen bonding between the protonated dimethylamino group and the oxygen of the imidazolidinone ring. The spatial relationship between the amine nitrogen and phenyl ring in this conformation allows proper fit of imidoline with key dimensions described for the dopamine receptor.

Mazapertine (RWJ-37796) is an arylpiperazine antipsychotic with high affinity to dopamine D2 and D3, serotonin 5-HT1A and alpha 1A-adrenergic receptors. It was being studied in the treatment of schizophrenia.

Etorphine was the first potent opiate agonist employed primarily for use in non-domestic and wild species. Etorphine was 500 times as potent as morphine, with a very rapid onset and short duration of action. In morphine-dependent subjects, etorphine suppressed abstinence but for a shorter period than morphine. Etorphine is a full opiate agonist and binds to multiple opiate sites in the central nervous system. It is believed to produce its clinical effects through binding the µ-, δ-, and κ- opiate sites. It has a potent effect on depressing the respiratory centers of the CNS thus resulting in apnea being commonly seen in immobilized animals. Etorphine revolutionized the ability of biologists and veterinarians to safely capture and restrain many species that previously could not be handled. Etorphine is not currently commercially available due to lack of production by the manufacturer.

Volinanserin (MDL-100,907) is a highly selective 5-HT2A receptor antagonist. It is widely used in scientific research to investigate the function of the 5-HT2A receptor. Volinanserin is also being trialed as a potential antipsychotic, antidepressant and treatment for insomnia. Volinanserin (M-100907) was in phase III trials for chronic schizophrenia. In August 1999, development was discontinued for acute schizophrenia (schizoaffective disorder) on the basis of poor results. M-100907 is also active in animal models involving blockade of NMDA glutamatergic channel receptors, an effect known to resemble some behavioral symptoms of schizophrenia in man. M-100907 is also claimed in other patents for the treatment of thromboembolic disorders, for the treatment of various developmental neurological disorders such as autism and attention deficit hyperactivity disorder.

Banoxantrone (formally known as AQ4N), a bioreductive drug that is irreversibly converted to AQ4, a stable DNA affinic cytotoxic compound. Banoxantrone is activated by haem-containing reductases such as inducible nitric oxide synthase (iNOS). In hypoxic cells, AQ4N is reduced to the topoisomerase II inhibitor AQ4. By inhibition of topoisomerase II within these hypoxic areas, AQ4N has been shown to sensitize tumors to existing chemo- and radiotherapy treatments. Novacea, the company which was responsible for clinical trials for banoxantrone had decided to scale back on its clinical development, including discontinuing the clinical trial in acute lymphoblastic leukemia and delaying the planned clinical trial in B-cell lymphoma. The company decided to continue enrollment in an ongoing Phase 1b/2a clinical trial in patients with glioblastoma multiforme. However, further information about these clinical trials are not available. Some recent experiments have shown that targeting hypoxic tumors with high levels of iNOS with a combination of AQ4N and radiotherapy could be a useful clinical therapeutic strategy.

BMS-754807 is a small-molecule insulin-like growth factor 1 receptor (IGF-1R) antagonist that was being developed by Bristol-Myers Squibb. BMS-754807 is a potent and reversible inhibitor of the insulin-like growth factor 1 receptor/insulin receptor family kinases (Ki, <2 nmol/L). It is currently in phase II development for the treatment of a variety of human cancers. BMS-754807 effectively inhibits the growth of a broad range of human tumor types in vitro, including mesenchymal (Ewing's, rhabdomyosarcoma, neuroblastoma, and liposarcoma), epithelial (breast, lung, pancreatic, colon, gastric), and hematopoietic (multiple myeloma and leukemia) tumor cell lines (IC50, 5-365 nmol/L); the compound caused apoptosis in a human rhabdomyosarcoma cell line, Rh41, as shown by an accumulation of the sub-G1 fraction, as well as by an increase in poly ADP ribose polymerase and Caspase 3 cleavage. BMS-754807 is active in vivo in multiple (epithelial, mesenchymal, and hematopoietic) xenograft tumor models with tumor growth inhibition ranging from 53% to 115% and at a minimum effective dose of as low as 6.25 mg/kg dosed orally daily. Combination studies with BMS-754807 have been done on multiple human tumor cell types and showed in vitro synergies (combination index, <1.0) when combined with cytotoxic, hormonal, and targeted agents. The combination of cetuximab and BMS-754807 in vivo, at multiple dose levels, resulted in improved clinical outcome over single agent treatment. These data show that BMS-754807 is an efficacious, orally active growth factor 1 receptor/insulin receptor family-targeted kinase inhibitor that may act in combination with a wide array of established anticancer agents.

Indotecan (LMP400) is a novel indenoisoquinoline derivative with specific topoisomerase I inhibition activity, developed by Division of Cancer Treatment and Diagnosis National Cancer Institute for cancer treatment. In preclinical studied Indotecan inhibited the cell growth of established mouse pheochromocytoma cell lines and primary human tumor tissue cultures. Low doses of Indotecan decreased the protein levels of hypoxia-inducible factor 1 (HIF-1α), one of a family of factors studied as potential metastatic drivers in these tumors. In vitro, Indotecan showed an increase in the growth-inhibitory effects in combination with other chemotherapeutic drugs that are currently used for the treatment of pheochromocytoma. Recently Indotecan has entered Phase I clinical trials for the treatment of cancer patients at the National Cancer Institute, and definite plans are being formulated to commence Phase II clinical trials.