Omtriptolide (previously known as PG490-88 or F60008), an immunosuppressant that has been shown to be the safe and potent antitumor agent and it has been approved entry into Phase I clinical trial for the treatment of prostate cancer in the USA. In addition, the drug is participating in phase I clinical trial for the treatment of myeloid leukemia. Experiments on animals have shown omtriptolide was highly effective in the prevention of murine graft-versus-host disease (GVHD). The immunosuppressive effect of the drug was mediated by inhibition of alloreactive T cell expansion through interleukin-2 production. However, this study was discontinued. Recently published article has shown omtriptolide possesses the potential as a prophylactic agent to prevent ischemia/reperfusion (I/R)-induced lung injury.

Hydroxytamoxifen (Afimoxifene) is an active metabolite of tamoxifen exerting estrogen receptor modulatory function. In addition, hydroxytamoxifen binds to regulates transcriptional activity of the estrogen-related receptor gamma. ASCEND Therapeutics, Inc. was developing TamoGel (4-hydroxytamoxifen gel) for a variety of estrogen-dependent conditions, including breast cancer, cyclic breast pain and gynecomastia.

Omtriptolide (previously known as PG490-88 or F60008), an immunosuppressant that has been shown to be the safe and potent antitumor agent and it has been approved entry into Phase I clinical trial for the treatment of prostate cancer in the USA. In addition, the drug is participating in phase I clinical trial for the treatment of myeloid leukemia. Experiments on animals have shown omtriptolide was highly effective in the prevention of murine graft-versus-host disease (GVHD). The immunosuppressive effect of the drug was mediated by inhibition of alloreactive T cell expansion through interleukin-2 production. However, this study was discontinued. Recently published article has shown omtriptolide possesses the potential as a prophylactic agent to prevent ischemia/reperfusion (I/R)-induced lung injury.

Pozanicline is an alpha4-beta2 neuronal nicotinic receptor partial agonist. It had been in phase II clinical trials for the treatment of attention hyperactivity disorder and Alzheimer’s disease. It was tested for the treatment of schizophrenia too. All these studies were discontinued. Modulation of hippocampal learning and memory using Pozanicline in animal model was effective as novel therapeutic strategies for nicotine addiction. However future clinical trial was terminated.

Saracatinib (AZD0530) is an oral, dual inhibitor of c-Src/Abl kinases initially developed by AstraZeneca for the treatment of cancer. The drug was tested for many neoplasms and reached phase III for ovarian cancer (in combination with paclitaxel), however without demonstrating any significant effect. Sarcatinib is also tested in patients with Alzheimer's Disease (Phase II). Its effect on Alzheimer's Disease patients is explained by inhibition of another kinase, Fyn, which is highly expressed in brain.

Brivanib is a pyrrolotriazine-based compound and an inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) with potential antineoplastic activity. It specifically targets and strongly binds to human VEGFR-2, a tyrosine kinase receptor and pro-angiogenic growth factor expressed almost exclusively on vascular endothelial cells. Blockade of VEGFR-2 by this agent may lead to an inhibition of VEGF-stimulated endothelial cell migration and proliferation, thereby inhibiting tumor angiogenesis. Brivanib has a moderate potency compared to VEGFR-2 against VEGFR-1 and FGFR-1 as well. Brivanib is suggested to be efficient in treatment of hepatocellular carcinoma (HCC). As first-line and as second-line therapy brivanib demonstrated promising antitumor activity and a manageable safety profile in patients with advanced, unresectable HCC in phase II clinical trials. On 3 march 2011, orphan designation was granted by the European Commission to Bristol-Myers Squibb for brivanib alaninate for the treatment of hepatocellular carcinoma.[

Nemorubicin, a doxorubicin derivative, is a DNA-intercalator, topoisomerase and RNA synthesis inhibitor that was undergoing development with Nerviano Medical Sciences (Nerviano MS; formerly Pharmacia Italia) for the treatment of solid tumours, specifically, the loco-regional treatment of primary liver tumours (hepatocellular carcinoma). The drug is active on tumors resistant to alkylating agents, topoisomerase II inhibitors and platinum derivatives. It works primarily through topoisomerase I inhibition. Of note, Nemorubicin is active in cells with upregulation of the nucleotide excision repair (NER) pathway, where current therapies fail. Nemorubicin is biotransformed in the liver into cytotoxic metabolites that may further contribute to render this drug highly active against primary liver tumors or liver metastases. Clinical trials were conducted in Europe, US and China with Nemorubicin given at different dose-schedules and by different routes of administration: as single agent by systemic IV route, oral route and by intra-hepatic artery (IHA) infusion alone or in combination with cisplatin.

GV 150526A (gavestinel) is an investigational drug for a neuroprotective therapy of acute ischemic stroke within 6 hours of symptom onset. It is a potent and selective non-competitive antagonist at the glycine site of the N-methyl-D-aspartate receptor (NMDA) which reduces infarct volume in experimental stroke models. Gavestinel acts at the strychnine-insensitive glycine binding site of the NMDA receptor-channel complex with nanomolar affinity (pKi = 8.5), coupled with high glutamate receptor selectivity. Gavestinel displays higher than 1000-fold selectivity over NMDA, AMPA and kainate binding sites and is orally bioavailable and active in vivo. GV 150526A inhibited convulsions induced by NMDA in mice, when administered by both IV and po routes (ED50 = 0.06 and 6 mg/kg, respectively). The safety and efficacy of GV150526 were studied in two phase III randomized placebo-controlled clinical trials of acute ischemic stroke patients within 6 h from onset [The Glycine Antagonist in Neuroprotection (GAIN) International and GAIN Americas Trials] sponsored by GlaxoSmithKline. The results of these trials suggested that gavestinel was not of substantial benefit or harm to patients with primary intracerebral hemorrhage.

Alvameline is a partial agonist of the M1 mAChR that also displays M2/M3 antagonist effects. It readily crosses the blood-brain barrier. It has an effect profile that makes it of interest to test its ability to counteract bladder overactivity in humans. Behaviorally, alvameline has been shown to significantly improve Morris water maze (MWM) performance in both young and ageimpaired rats. It failed to improve cognition in patients with mild to moderate Alzheimer's disease.

Gepotidacin (formerly GSK2140944) is a novel, first-in-class, triazaacenaphthylene antibacterial that selectively inhibits bacterial DNA gyrase and topoisomerase IV by a unique mechanism, one that is not utilized by any currently approved human therapeutic agent. As a consequence of its novel mode of action, gepotidacin is active in vitro against target pathogens carrying resistance determinants to established antibacterials, including fluoroquinolones. Gepotidacin has demonstrated in vitro activity against key pathogens, including drug-resistant strains, associated with a range of conventional and biothreat infections. GlaxoSmithKline is developing Gepotidacin for the treatment of gonorrhoea and skin and soft tissue infections.