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).

Pentamoxane was developed as a tranquilizer. Information about the further development of this compound is not available.

Bioresmethrin is a synthetic pyrethroid insecticide. It is the (+)-trans isomer of resmethrin which itself contains a minimum of 30% bioresmethrin. Bioresmethrin is the [1R, trans] isomer of resmethrin and has greater insecticidal activity than the racemic mixture. Bioresmethrin is a potent contact insecticide effective against a wide range of household insects, plant pests, grain pests and insects found in animal housing. It exhibits a high order of insecticidal activity, which when coupled with its excellent toxicological properties, makes it potentially one of the safest and most useful insecticides now being produced.

SNX-5422 (also known as PF-04929113) is a synthetic, novel, small molecule Hsp90 inhibitor with potential antineoplastic activity. Hsp90 is a molecular chaperone that plays a key role in the conformational maturation of oncogenic signaling proteins, such as HER2/ERBB2, AKT, RAF1, BCR-ABL, and mutated p53, as well as many other molecules that are important in cell cycle regulation or immune responses. Inhibition of Hsp90 by SNX-2112 may result in the proteasome degradation of oncogenic client proteins, including HER2/ERBB2, and the inhibition of tumor cell proliferation. SNX-5422 is originally developed by Pfizer and Serenex, Inc., and the phase I clinical trials for it has been completed in the treatment of solid tumors. Although the mechanism of action remains to be fully elucidated, SNX-5422, which is a prodrug, is rapidly converted to SNX-2112 that accumulates in tumors relative to normal tissues.

PF-04531083 is selective Nav1.8 blocker. It has been investigated for the treatment of chronic pain, heart pain, post-surgical dental pain. However, these trials were discontinued.

MLN8054 is a reversible, ATP competitive inhibitor of recombinant Aurora A, developed by Millennium Pharmaceuticals. MLN8054 was tested in phase I clinical trials against advanced solid tumors. Reversible somnolence probably due to off-target inhibition of alpha-1 subunit of GABA-A receptor was dose limiting and prevented achievement of plasma concentrations predicted necessary for target modulation.