Picoplatin is a sterically hindered platinum (II) complex with antineoplastic properties developed for the treatment of cis-platin-resistant cancer. Picoplatin alkylates DNA, forming both inter- and intra-strand cross-linkages, resulting in inhibition of DNA replication and transcription, and the induction of apoptosis. However, in Phase III trials, picoplatin failed to meet its primary endpoint for advanced cell lung cancer. It remains in development for other cancers.

MK-2866 (Gtx-024) is a selective androgen receptor modulator (SARM) for treatment of conditions such as muscle wasting and osteoporosis. It is a non-steroidal agent with anabolic activity designed to work like testosterone, thus promoting and/or maintaining libido, fertility, prostate growth, and muscle growth and strength. Mimicking testosterone's action, this agent may increase lean body mass, thereby ameliorating muscle wasting in the hypermetabolic state of cancer cachexia.

Bicifadine (DOV-220075) is not a narcotic and is well-tolerated and, in preclinical studies, has been shown not to act at any opiate receptor, but inhibits monoamine neurotransmitter uptake by recombinant human transporters in vitro with a relative potency of norepinephrine:serotonin:dopamine of 1:2:17. Bicifadine was in Phase II clinical trial for pain caused by diabetic neuropathy, in addition, was in phase III clinical trial to treat Chronic Low Back Pain, but that studies were discontinued

Priralfinamide, also known as Ralfinamide, FCE-26742A; NW-1029; PNU-0154339E, is a Na-channel blocker for the treatment of neuropathic pain and other pain conditions such as post-operative dental pain. It has a relatively complex pharmacology, acting as a mixed voltage-gated sodium channel blocker (including Nav1.7), N-type calcium channel blocker, noncompetitive NMDA receptor antagonist, and monoamine oxidase B inhibitor. Priralfinamide is in phase Ⅲ clinical trials by Newron for the treatment of chronic neuropathic pain.

Taranabant is a highly selective cannabinoid-1 (CB1) receptor inverse agonist developed by Merck & Co for the treatment of obesity. The Phase III taranabant study involved about 2,400 patients and was to be conducted for two years. In March 2008, after completion of 52 weeks of the study, Merck reported positive results of the drug in conjunction with diet and exercise in obese patients. The patients experienced double the amount of weight loss by taking 2mg of taranabant when compared to the patients treated with placebo. However, in October 2008, the company discontinued the Phase III programme and clinical development of taranabant because of its side effects. The drug showed gastrointestinal and psychiatric side effects such as increased anxiety, depression and irritability. Merck had previously planned to file for regulatory approval with the US Food and Drug Administration in 2008, but subsequently withdrew it.

Linifanib (ABT-869) is a structurally novel, receptor tyrosine kinase (RTK) inhibitor that is a potent inhibitor of members of the vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptor families, but has much less activity against unrelated RTKs, soluble tyrosine kinases, or serine/threonine kinases. Linifanib (ABT-869) does not have a general antiproliferative effect due to its high dose requirement. However, it may exhibit potent antiproliferative and apoptotic effects on tumor cells whose proliferation is dependent on mutant kinases, such as FMS-related tyrosine kinase receptor-3 (FLT3). Linifanib (ABT-869) was in phase III clinical trial for the treatment of hepatocellular carcinoma, but the study failed to meet the primary end point.

Piclidenoson (CF101), generically known as IB-MECA (methyl 1-[N6-(3-iodobenzyl)-adenin-9-yl]-b-D-ribofuronamide), is an oral small molecule drug formulated in a tablet. The activity of CF101 as an anti-inflammatory agent has been tested in a number of different experimental models including adjuvant and collagen induced arthritis and inflammatory bowel disease. CF101 is a highly specific agonist at the A3AR known to induce a robust anti-inflammatory effect in different experimental animal models. The CF101 mechanism of action entails down-regulation of the NF-κB-TNF-α signaling pathway, resulting in inhibition of pro-inflammatory cytokine production and apoptosis of inflammatory cells. Piclidenoson is currently being developed for the treatment of autoimmune inflammatory diseases like RA and psoriasis, hoping to replace the current standard of care, methotrexate (MTX). Can-Fite has tested CF101 in a number of Phase II studies in different diseases. A Phase II study in Psoriasis successfully met its primary endpoint showing that CF101 effectively ameliorated disease symptoms. In an interim analysis of the Phase II/III study the data justified full enrollment of the study. Phase II studies in Rheumatoid Arthritis (RA) demonstrated efficacy of CF101 given as a monotherapy. Moreover, a direct correlation between A3AR at baseline and patients’ response to CF101, suggesting its utilization as a predictive biomarker. Piclidenoson is headed into Phase 3 trials for RA and psoriasis.

Dexverapamil (R-verapamil) is an enantiomer of verapamil. R-isomer behaved as an inhibitor of multidrug-resistant protein MRP1 (involved in the cancer cell multidrug resistance phenotype). It was developed by Knoll (BASF Pharma) as a chemosensitiser and/or modulator of multidrug resistance for use in combination with cancer chemotherapy. Dexverapamil was undergoing phase II clinical studies in France, Italy, Spain, United Kingdom and the US in patients with various cancers. It was also undergoing phase I clinical trials in Japan where it was licensed to Mitsui and Mitsui Toatsu Chemicals. However, development was discontinued. Dexverapamil (R-verapamil) has been developing by AGI therapeutics for the treatment of Irritable bowel syndrome however development was discontinued.

Cilengitide is a cyclized Arg-Gly-Glu (RGD)-containing pentapeptide that selectively blocks activation of the αvβ3 and αvβ5 integrins. Its precursor was first synthesized in 1995 as c(RGDfV), and later modified by the incorporation of N-methyl Val c(RGDfMetV), generating the current form of the drug. Cilengitide displays subnanomolar antagonistic activity for αvβ3 and αvβ5, and is the first integrin antagonist evaluated in clinical phase I and II trials for treatment of glioblastoma and several other tumor types. Cilengitide-induced glioma cell death and inhibition of blood vessel formation may use different molecular mechanisms, including regulation of tumor hypoxia and activation of apoptotic pathways. Cilengitide inhibits cell signaling through FAK-Src-Akt and Erk mediated pathways in endothelial and tumor cells and attenuates the effect of VEGF stimulation on growth factor signaling. Cilengitide has shown encouraging activity in patients with glioblastoma as single agent, and in association with standard RT and temozolomide.

Aleglitazar is a dual agonist of PPARalpha/PPARgamma which was developed by Hoffmann-La Roche for the treatment of type 2 diabetes. Aleglitazar activates PPAR receptors with EC50 in nanomolar range and exerts a cardioprotective effect in vitro. The drug is currently in phase III of clinical trials.