Fonturacetam, also known as Phenylpiracetam, is marketed in Russia as Carphedon and Phenotropil. It is one of the first ever nootropic drugs and originally discovered in Russia. Fonturacetam acts on most neurotransmitter systems and has been used for its cognitive and physical enhancing properties, and also as an antidepressant.

JNJ-26854165 (Serdemetan), a novel tryptamine derivative, was developed as an activator of p53, and its initially proposed mechanism of action involved preventing the association of HDM2 with the proteasome and thereby stabilizing HDM2 substrates such as p53. Consistent with this proposed mechanism, Serdemetan induced apoptosis in acute myeloid and lymphoid leukemia cell lines and in primary acute leukemia isolates. Serdemetan is currently being evaluated in Phase I clinical trials in patients with non-small cell lung cancer; prostate cancer; solid tumours.

Albitiazolium (SAR97276) is a clinical antimalarial candidate from a series of choline analogs designed to inhibit plasmodial phospholipid metabolism. Albitiazolium exerts powerful in vitro and in vivo antimalarial activities. Albitiazolium has been shown to have appropriate pharmacokinetic and safety parameters in humans and it was being tested in phase II clinical trials by Sanofi, with confirmed antimalarial activity in adult patients. However, Sanofi discontinued development of Albitiazolium.

Veliparib (ABT-888) is a potent inhibitor of PARP, has good oral bioavailability, can cross the blood-brain barrier, and potentiates temozolomide, platinums, cyclophosphamide, and radiation in syngeneic and xenograft tumor models. AbbVie is developing veliparib for the treatment of cancers. Clinical trials are underway worldwide, investigating veliparib primarily as part of a combination therapy in oncology indications such as brain, colorectal, melanoma, ovarian, prostate and pancreatic cancers.

Lirequinil is a benzoquinolizinone derivative. It is a partial agonist to the benzodiazepine (BDZ) receptor. Lirequinil slightly lowered the rhythmic slow-wave activity frequency during waking mobility. Lirequinil acts more selectively than nitrazepam to promote the drowsy EEG pattern, and the partial agonistic properties may minimize the residual effects during waking mobility similar to the short-acting agent zopiclone. Lirequinil was well tolerated at all doses, causing no clinically relevant changes in vital signs or laboratory parameters. At doses of 10 and 30 mg there were signs of unsteady gait, indicating a central nervous system depressant effect. Lirequinil had been in phase II for the treatment of sleep disorders.

Levcycloserine is a general inhibitor of pyridoxal 5'-phosphate (PLP)-dependent enzymes. It is an excellent inhibitor of threonine deaminase and serine palmitoyltransferase. Levcycloserine is a ceramide synthesis inhibitor. Levcycloserine is a selective antitumoral agent for neuroblastoma and medulloblastoma cells with the ability to reduce expression of tumour associated gangliosides. In vivo experiments suggest that levcycloserine may be effective drug for treatment of neuroblastoma and medulloblastoma. Levcycloserine interferes with the life cycle of HIV. Levcycloserine selectively down-modulated CD4 expression without affecting the expression of CD3 and CD8. Levcycloserine also inhibited T cell mitogen responses without affecting IL-2 production. Selective inhibition of CD4 by levcycloserine together with its antiviral effects may offer a novel approach for interfering with HIV cell binding and infectivity.

Dilopetine is a racemic mixture of (+)-E-6006 citrate (E-6101) and (-)-E6006 citrate (E-6102) enantiomers being developed as a potential antidepressant. Initial experiments indicate that dilopetine exhibits an antidepressant profile in tests with mice and rats. Dilopetine has been observed to normalize the increased substance P levels in the periaqueductal gray of rats during stressor exposure (Hamon, personal communication), suggesting that the drug may function by inhibiting substance P release. Treatment with dilopetine reduced the vocalizing of isolated guinea pig pups in a dose-dependent fashion.

Lidadronic acid is the calcium metabolism regulator.

Banoxantrone (formally known as AQ4N), a bioreductive drug that is irreversibly converted to AQ4, a stable DNA affinic cytotoxic compound. Banoxantrone is activated by haem-containing reductases such as inducible nitric oxide synthase (iNOS). In hypoxic cells, AQ4N is reduced to the topoisomerase II inhibitor AQ4. By inhibition of topoisomerase II within these hypoxic areas, AQ4N has been shown to sensitize tumors to existing chemo- and radiotherapy treatments. Novacea, the company which was responsible for clinical trials for banoxantrone had decided to scale back on its clinical development, including discontinuing the clinical trial in acute lymphoblastic leukemia and delaying the planned clinical trial in B-cell lymphoma. The company decided to continue enrollment in an ongoing Phase 1b/2a clinical trial in patients with glioblastoma multiforme. However, further information about these clinical trials are not available. Some recent experiments have shown that targeting hypoxic tumors with high levels of iNOS with a combination of AQ4N and radiotherapy could be a useful clinical therapeutic strategy.

BMS-754807 is a small-molecule insulin-like growth factor 1 receptor (IGF-1R) antagonist that was being developed by Bristol-Myers Squibb. BMS-754807 is a potent and reversible inhibitor of the insulin-like growth factor 1 receptor/insulin receptor family kinases (Ki, <2 nmol/L). It is currently in phase II development for the treatment of a variety of human cancers. BMS-754807 effectively inhibits the growth of a broad range of human tumor types in vitro, including mesenchymal (Ewing's, rhabdomyosarcoma, neuroblastoma, and liposarcoma), epithelial (breast, lung, pancreatic, colon, gastric), and hematopoietic (multiple myeloma and leukemia) tumor cell lines (IC50, 5-365 nmol/L); the compound caused apoptosis in a human rhabdomyosarcoma cell line, Rh41, as shown by an accumulation of the sub-G1 fraction, as well as by an increase in poly ADP ribose polymerase and Caspase 3 cleavage. BMS-754807 is active in vivo in multiple (epithelial, mesenchymal, and hematopoietic) xenograft tumor models with tumor growth inhibition ranging from 53% to 115% and at a minimum effective dose of as low as 6.25 mg/kg dosed orally daily. Combination studies with BMS-754807 have been done on multiple human tumor cell types and showed in vitro synergies (combination index, <1.0) when combined with cytotoxic, hormonal, and targeted agents. The combination of cetuximab and BMS-754807 in vivo, at multiple dose levels, resulted in improved clinical outcome over single agent treatment. These data show that BMS-754807 is an efficacious, orally active growth factor 1 receptor/insulin receptor family-targeted kinase inhibitor that may act in combination with a wide array of established anticancer agents.