Fozivudine tidoxil is a thioether lipid–Zidovudine (ZDV) conjugate. After intake it is split intracellularly into the lipid moiety and ZDV-monophosphate, which is subsequently phosphorylated to the active metabolite ZDV-triphosphate. The rationale behind the development of fozivudine (FZD) was to take advantage of the high cleavage activity in mononuclear cells and other organs resulting in increased amounts of intracellular ZDV available for phosphorylation to the active metabolite, and a very low activity in red blood and stem cells, which should result in reduced haematologic toxicity. It is member of the family of nucleoside reverse transcriptase (RT) inhibitors. Fozivudine tidoxil has been in Phase II clinical trials for the treatment of HIV infection. There were three adverse events possibly related to fozivudine: urine abnormality, gastrointestinal pain and abnormal dreams.

Rislenemdaz, also known as MK-0657 or CERC‐30, is an orally active, selective NMDA receptor subunit 2B (NR2B) antagonist which was a study for the treatment of Parkinson's disease and major depressive disorder (MDD). The data from the phase I clinical trials have shown that drug was not effective in improving motor symptoms in patients with Parkinson disease. In case of using this drug to treat MDD, in spite of the Missing Primary Endpoint in phase II clinical trials, it was shown, that MK-0657 had possessed a potential clinical meaningfulness, that is why it was suggested to continue studying it for MDD patients.

Pfizer was developing PF-04991532, a potent and selective hepatoselective glucokinase activator. PF-04991532 ameliorates hyperglycemia without causing hepatic steatosis in diabetic rats. F-04991532 reduced plasma glucose concentrations independent of changes in insulin concentrations in a dose-dependent manner both acutely and after 28 days of sub-chronic treatment. PF-04991532 may offer glycemic control without inducing hepatic steatosis supporting the evaluation of tissue specific activators in clinical trials. In 2012, Pfizer discontinued the development of the compound.

Puerarin (7, 4’-dihydroxyisolavone-8-β-glucopyranoside) is an active isoflavone extracted from the roots of Pueraria lobata (Willd.) Ohwi. Puerarin is widely used in traditional Chinese medicine, and is clinically used in China for the treatment of coronary artery disease, heart failure, hypertension and myocardial infarction. It has been reported that puerarin had therapeutic effects on diabetes mellitus, arteriosclerosis and myocardial ischemia in animals. Puerarin demonstrated beta-adrenergic receptor blocking effect. On the other hand, puerarin stimulated alpha1-adrenoreceptor to increase glucose uptake into cultured C2C12 cells of mice. Puerarin has been investigated for the treatment (phase II clinical trials) of Alcohol Abuse, Rheumatoid Arthritis and Hypertension.

Apitolisib, a dual inhibitor of mTOR and phosphatidylinositol 3-kinase (PI3K), was being developed by Roche and Genentech as an orally administered therapy of cancer. Apitolisib is a selective, potent, orally bioavailable inhibitor of Class I PI3 kinase (PI3K) and mTOR kinase (TORC1/2) with excellent pharmacokinetic and pharmaceutical properties. Apitolisib displayed excellent potency against class I PI3K isoforms (IC50 PI3K-α, β, δ and γ = 4.8, 27, 6.7 and 14 nM) and mTOR kinase (IC50 = 17 nM) and selectivity against a large panel of other kinases. Apitolisib is in phase II trials by Genentech for the treatment of breast cancer, prostate cancer, endometrium cancer, kidney cancer. However, no recent development has been reported. It is also in phase I trials by Genentech for the treatment of non-Hodgkin's lymphoma.

AstraZeneca was developing AZD-2066, a metabotropic glutamate receptor 5 (mGLUR5) antagonist, for the oral treatment of pain indications (e.g. chronic neuropathic pain and painful diabetic neuropathies), depressive disorders and gastro-oesophageal reflux disease. AZD-2066 had been in phase II clinical trials by AstraZeneca for the treatment of diabetic neuropathic pain and phase I for the treatment of gastrooesophageal reflux disease (GERD). However, this reasearch had being discontinued.

MK-8776 (SCH900776) is inhibitor of CHK1. It was tested in clinical trials against acute myeloid leukaemia, solid tumors and lymphoma.

Lomibuvir (VCH-222) is a novel, potent and selective inhibitor of non-nucleoside polymerase of the hepatitis C virus (HCV) RNA-dependent RNA polymerase, with an IC50 range of 0.94-1.2 μM. Lomibuvir was generated from ViroChem's research programme investigating HCV NS5B polymerase inhibitors. In phase 1 and 2 clinical studies, Lomibuvir demonstrated effective antiviral efficacy, with substantial reductions in plasma HCV RNA in patients chronically infected with genotype 1 HCV. On 15 May 2014 Vertex Pharmaceuticals completes a phase II trial in Hepatitis C (treatment-naive, combination therapy) in USA, Canada, Germany, Poland and United Kingdom (NCT01516918). On 26 Jul 2016 Trek Therapeutics acquires lomibuvir from Vertex Pharmaceuticals.

AT7519M or AT7519, a small molecule inhibitor of cyclin-dependent kinases 1, 2, 4, 5, and 9, participated in phase II clinical trials in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). As a result, in CLL, some patients had tumor reductions, but the objective response rate (ORR) was low. In MCL, activity was noted with ORR of 27%. In addition, AT7519M was studied in patients with previously treated multiple myeloma, to understand whether the drug alone or in combination with bortezomib were effective treatments. Recent experiments also have shown that AT7519 is a promising drug for the treatment of high-risk neuroblastoma patients with MYCN amplification. It is known, that MYCN-dependent neuroblastomas have low cure rates with current multimodal treatment.

Deoxyspergualin is a derivative of the antitumor antibiotic spergualin, that used as an immunosuppressive drug. Deoxyspergualin shows immunosuppressive activity both in vitro and in vivo, affecting B-lymphocyte, T-lymphocyte and macrophage/monocyte function. In rodents and human cell systems, Deoxyspergualin shows a dose-dependent inhibition of primary and secondary responses to T-, B- and antigen-presenting cell-dependent reactions. Deoxyspergualin also blocks nuclear translocation of NF-kB in a pre-B-cell line, thereby affecting NF-kB driven transcription of the kappa light chain. Deoxyspergualin inhibits desoxyhypusine synthase, the first enzyme in the formation of active eukaryotic translation initiation factor 5A. This factor is important for the stabilization of certain mRNA transcripts (TNF-a and others). The immunosuppressive properties of Deoxyspergualin have been demonstrated in preclinical animal studies including Systemic lupus erythematosus models. In humans with glucocorticoidresistant kidney transplant rejection, Deoxyspergualin shows the same efficacy rate as the strongly T-cell depleting anti-CD3 monoclonal antibody. Deoxyspergualin has been licensed in Japan for acute renal allograft rejection since 1994. In 2003, an open clinical trial successfully tested Deoxyspergualin in patients with persistent ANCA-associated vasculitis. Adverse events (AE) were common but rarely led to treatment discontinuation. Against this background, Deoxyspergualin was granted an orphan drug status for the treatment of Wegener’s granulomatosis by the European Medicines Agency (EMA).