Sonepiprazole exhibits highly specific binding to the D4 dopamine receptor with more than 100-fold selectivity for the D4 receptor over other receptors, including dopamine, serotonin, and adrenergic receptors. It is a neutral antagonist at the D4 dopamine receptor and is devoid of dopamine agonist activity. Sonepiprazole selectively induces c-fos expression in the prefrontal cortex and blocks behavioral, biochemical, and genomic effects of repeated amphetamine administration in rats. Sonepiprazole was investigated as an antipsychotic for the treatment of schizophrenia in a placebo-controlled clinical trial, but in contrast to its comparator olanzapine no benefits were found and it was not researched further for this indication.

Dasotraline, also known as SEP-225,289, is a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI). It has an extended half-life (47-77 hours) that supports the potential for plasma concentrations yielding a continuous therapeutic effect over the 24-hour dosing interval at steady state. Dasotraline has shown a lower potential for abuse than methylphenidate in clinical testing. Dasotraline was discovered by Sunovion Pharmaceuticals Inc. and is currently in development to evaluate its use in treating ADHD in adults and children, and BED in adults in the United States. It has not been approved by the U.S. Food and Drug Administration (FDA) for the treatment of ADHD, BED or any other disorder.

NMED-160 (also known as MK-6721, NP-118809, Z-160) is a potent N-type calcium channel blockers, which has good selectivity over L-type calcium channels. Neuromed Pharmaceuticals developed this compound for the treatment of the chronic pain. However, that study was discontinued in 2007 in spite of absence of adverse events, but because drug did not demonstrate the ideal, pharmaceutical characteristics considered necessary to advance the compound further in development. Then Zalicus, Inc. was developing that drug for the treatment of chronic neuropathic pain associated with lumbosacral radiculopathy and post-herpetic neuralgia and drug was in the phase II clinical trial. Nevertheless, based on the result from trials, where Z160 did not meet the primary endpoint, Zalicus was also discontinuing the Z160 program.

Zoniporide hydrochloride is a novel, potent and selective NHE-1 inhibitor (IC50 = 14 nM). Reduces infarct size in the isolated heart (EC50 = 0.25 nM). Attenuates post-ischemic cardiac contractile dysfunction and ischemia-reperfusion-induced ventricular fibrillation in vivo. Zoniporide hydrochloride represents a novel class of potent and selective human NHE-1 inhibitors with potential utility for providing cardioprotection in a clinical setting.

CI 1040 is an inhibitor of the mitogen-activated protein (MAP) kinase signal transduction pathway and has been shown to specifically inhibit MAP kinase kinase (MEK). CI 1040 was being developed by Parke-Davis (formerly a division of WarnerLambert, Now Pfizer) as an anticancer agent. It was the initial MEK inhibitor to undergo clinical evaluation based on promising preclinical activity. However, its development has been discontinued.

Tipifarnib is an oral farnesyltransferase (FTase) inhibitor which was developed by Janssen (J&J). Upon administration, tipifarnib inhibits FTase and thus suppresses the activity of downstream effectors. The drug reached phase III of clinical trials for such diseases as pancreatic cancer (terminated), colorectal cancer (terminated) and acute myeloid leukemia (in elderly patients).

Lintitript (SR 27897) is a selective cholecystokinin type A (CCK-A) receptor antagonist, which was initially developed by Sanofi for appetite disorders. It is known, that CCK modulates feeding and dopamine-induced behavior in the central and peripheral nervous system. Lintitript presumably alters feeding habits, however, the exact mechanism of action is not known. Lintitript was investigated in animals with anorexia nervosa, in addition, drug was in clinical trial for the patients with advanced pancreatic cancer, but these studies were discontinued.

BMS-582949 acts as a dual action kinase inhibitor. It inhibits both p38 mitogen-activated protein kinase (p38 MAPK) activity and activation of p38. As a blocking agent for activation of p38 kinase BMS-582949 appeared to be well suited to resist such cellular responses that would drive p38 activation more strongly. BMS-582949 is in Phase II clinical trials for the treatment of rheumatoid arthritis, psoriasis, and atherosclerosis.

R-etodolac (SDX-101) is the non-cyclooxygenase 2-inhibiting R-enantiomer of the non-steroid anti-inflammatory drug etodolac (1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid). The absolute configuration of the enantiomer is R-(-)-etodolac. R-etodolac specifically bound retinoid X receptor (RXRalpha), inhibited RXRalpha transcriptional activity, and induced its degradation by a ubiquitin and proteasome-dependent pathway. In addition R-etodolac can disrupt the beta-catenin signaling pathway. R-etodolac exerts antineoplastic properties. R-etodolac was in phase 2 studies for the treatment of hematologic malignancies however development was discontinued.

Taltobulin, also known as HTI-286 and SPA-110, is a fully synthetic analog of the natural tripeptide hemiasterlin, inhibits tubulin polymerization and circumvents transport-based resistance to taxanes. Taltobulin was a potent inhibitor of proliferation (mean IC50 = 4 nm in 18 human tumor cell lines) and had substantially less interaction with multidrug resistance protein (P-glycoprotein) than currently used antimicrotubule agents, including paclitaxel, docetaxel, vinorelbine, or vinblastine. Taltobulin showed strong antitumor activity both in androgen-dependent and androgen- independent tumors and may be a promising agent in second- line treatment strategies for patients suffering from docetaxel- refractory prostate cancer.