Nastorazepide (Z-360) is a selective, orally available, gastrin/cholecystokinin 2 (CCK-2) receptor antagonist with potential antineoplastic activity. Z-360 binds to the gastrin/CCK-2 receptor, thereby preventing receptor activation by gastrin, a peptide hormone frequently associated with the proliferation of gastrointestinal and pancreatic tumor cells. It is currently under development as a therapeutic drug for pancreatic cancer, gastroesophageal reflux disease and peptic ulcers. The most commonly reported adverse events were nausea, abdominal pain, vomiting and fatigue.

XK-469 (2-[4-(7-chloro-2-quinoxalinyloxy)phenoxy]-propionic acid) is a novel synthetic quinoxaline phenoxypropionic acid derivative. The R-isomer of XK-469 was approximately twice as effective as the S-isomer of XK-469R. R( )-isomers induce reversible protein DNA crosslinks in mammalian cells. It acts as a selective topoisomerase IIβ inhibitor. A phase I study was performed to determine the safety and pharmacokinetics of XK-469, (R)- in patients with various neoplasms.

GlaxoSmithKline was developing GSK-424887as a dual antagonist of the human neurokinin receptor 1 and inhibitor of the serotonin transporter. GSK 424887 participated in phase I clinical trials for the treatment of depressive disorder and anxiety disorder. However, further development of GSK 424887 apparently was discontinued.

BMS-191011, an opener of the cloned large-conductance, Ca2+-activated potassium (maxi-K) channel, demonstrated efficacy in in vivo stroke models, which led to its nomination as a candidate for clinical evaluation. Its maxi-K channel opening properties were consistent with its structural topology, being derived by combining elements from other known maxi-K openers. BMS-191011 demonstrated efficacy as an opener of the cloned large-conductance Ca2+-activated potassium (maxi-K) channel in in vivo stroke models

Daikenchuto (TU-100) is a traditional Japanese Kampo medicine composed of four crude drugs: dried Japanese pepper, processed ginger, ginseng radix and maltose powder. TU-100 is traditionally used in the treatment of chronic gastrointestinal disorders, and often prescribed to relieve abdominal pain, abdominal distention, Crohn’s disease, irritable bowel syndrome, adhesive ileus, and paralytic ileus. TU-100 improves gastrointestinal dysmotility and reduces serum CRP levels in patients with grade B liver damage after hepatectomy. TU-100 is an effective treatment option after hepatic resection in patients with liver cancer. Although the effects of TU-100 on gastrointestinal motility have been unexplored, recent studies have revealed its various other effects, including the following: firstly, an anti-inflammatory response through the selective inhibition of cyclooxygenase-2 (COX-2) and/or down-regulation of several inflammatory mediators such as tumor necrosis factor-a, interleukin-1b and endothelin-1; secondly, the prevention of bacterial translocation; and thirdly, the increase of gastrointestinal blood flow through the induction of calcitonin gene-related peptide (CGRP), substance P and vasoactive intestinal polypeptide (VIP). TU-100, which is manufactured by Tsumura & Co. (Tokyo, Japan), has been approved by the US Food and Drug Administration as an investigational drug, and several placebo-controlled double-blind trials have been launched in the US to investigate its use for constipation and Crohn’s disease. TU-100 was approved for manufacture as a prescription drug in 1986 by the Japanese Ministry of Health and Welfare and has been sold commercially as a prescription Kampo (a generic term for the system of traditional medicine that was developed in Japan after being introduced from China in the fourth century) drug in Japan for many years.

Motesanib (AMG 706), a novel nicotinamide, was identified as a potent, orally bioavailable inhibitor of the VEGFR1/Flt1, VEGFR2/kinase domain receptor/Flk-1, VEGFR3/Flt4 and Kit receptors. Motesanib was expected to reduce vascular permeability and blood flow in human tumours. A phase III trial of motesanib in combination with paclitaxel and carboplatin in non-squamous NSCLC has been terminated by Takeda and subsequently the development was discontinued. Motesanib has also been investigated up to phase II in breast, thyroid, colorectal and gastrointestinal stromal tumours. However, development has been discontinued in these indications.