Pibaxizine is diphenylmethyl piperazine derivatives. It is a histamine H1 receptor antagonist. Animal experiments have shown that it has spasmolytic properties for smooth muscle, particularly in the bronchi, as well as anticholinergic and anti-serotonin activities. It can be concluded that Pibaxizine has a strong protective effect against bronchospasm caused by inhalation of a histamine aerosol. Protection against methacholine-induced bronchospasm was less marked. Pibaxizine had been in phase II clinical trial for the treatment of chronic obstructive pulmonary disease. However, this development was discontinued.

CC-401 is a potent inhibitor of all three forms of c-Jun N-terminal Kinase (JNK) (Ki of 25 to 50 nM) and has at least 40-fold selectivity for JNK compared with other related kinases. Celgene was developing CC 401 for the treatment of cancer and inflammatory disorders. CC 401 was being developed in an IV formulation and was in a phase I trial in patients with refractory acute myelogenous leukaemia. However, trials have ended and the company is not pursuing CC 401, but will advance other JNK inhibitors.

Binfloxacin is a topoisomerase inhibitor that was studied as an antibacterial agent.

Tenilsetam (CAS 997: ( /-)-3-(2-thienyl)-2-piperazinone), a cognition-enhancing drug successfully used for the treatment of patients suffering from Alzheimer's disease. According to the mechanism proposed, it inhibits advanced glycation end-product (AGE) formation. The beneficial effect of tenilsetam in Alzheimer's disease could come from the interference with AGE-derived crosslinking of amyloid plaques and a decreased inflammatory response to diminished activation of phagocytosing microglia. In addition was shown, that the long-term treatment with tenilsetam inhibited the formation of acellular capillaries without correcting pericyte loss. Was suggested that tenilsetam could be useful for the treatment of early diabetic retinopathy, but then these studies were discontinued.

R1530 is the multikinase inhibitor with potential antiangiogenesis and antineoplastic activities. R1530 is also a mitosis-angiogenesis inhibitor (MAI) that inhibits multiple receptor tyrosine kinases involved in angiogenesis, such as vascular endothelial growth factor receptor (VEGFR)-1, -2, -3, platelet-derived growth factor receptor (PDGFR) beta, FMS-like tyrosine kinase (Flt)-3, and fibroblast growth factor receptor (FGFR) -1, -2. In addition, this agent exhibits anti-proliferative activity by initiating mitotic arrest and inducing apoptosis. In the presence of R1530, polyploid cancer cells underwent apoptosis or became senescent which translated into potent in vitro and in vivo efficacy. Normal proliferating cells were resistant to R1530-induced polyploidy thus supporting the rationale for cancer therapy by induced polyploidy. Mitotic checkpoint kinase BubR1 was found downregulated during R1530-induced exit from mitosis, a likely consequence of PLK4 inhibition. R1530 strongly inhibited human tumor cell proliferation and growth factor-driven proliferation of endothelial and fibroblast cells. Significant tumor growth inhibition was demonstrated in a lung cancer xenograft model with a range of once daily, weekly and twice-weekly doses of R1530. Daily doses were most effective in the lung cancer model and also had significant growth inhibitory effects in models of colorectal, prostate, and breast tumors. Tumor regression occurred in all models treated with the maximum tolerated daily dose. The doses of 25 and 50 mg/kg QD resulted in biologically significant increased survival in all tested models. After oral administration in nude mice, R1530 showed good tissue penetration. R1530 had been in phase I clinical trials by Hoffmann-La Roche, Inc. for the treatment of advanced solid tumors. However, the clinical development of R1530 was discontinued.

Pilaralisib (XL147, SAR245408) is a potent and highly selective inhibitor of class I phosphatidylinositol 3-kinase (PI3K) (α, β, γ, and δ). In cellular assays, XL147 inhibits the formation of PIP3 in the membrane, and inhibits phosphorylation of AKT, p70S6K, and S6 in multiple tumor cell lines with diverse genetic alterations affecting the PI3K pathway. In a panel of tumor cell lines, XL147 inhibits proliferation with a wide range of potencies, with evidence of an impact of genotype on sensitivity. Repeat-dose administration of XL147 results in significant tumor growth inhibition in multiple human xenograft models in nude mice. Pilaralisib, was being developed by Exelixis and its licensee, Sanofi (formerly sanofi-aventis), for the treatment of solid tumours. However, the product was not listed on Sanofi's early stage pipeline as of end of July 2015 and there have been no recent reports on development identified.

Kynurenic acid is a product of the normal metabolism of amino acid L-tryptophan which has been shown to have a neuroactive profile. It exhibits activity against NMDA receptors and Neuronal acetylcholine receptor subunit alpha-7. It has been investigated as a potential therapeutic compound and as a biomarker in a number of neurological disorders. Although Kenyruic acid exhibits a poor penetration of the blood-brain barrier, it remains to be of particular interest to those researching Schizophrenia.

Rolafagrel (FCE 22178) is a selective thromboxane synthase inhibitor that has been evaluated for use in the treatment of diabetic nephropathy and thrombosis. Rolafagrel inhibits platelet and glomerular thromoxane synthase in animal and human kidney disease. A phase I clinical trial did not report drug-related adverse events. No information is available on current use of rolafagrel.

Piclamilast (RP 73401), is a selective PDE4 inhibitor. It is comparable to other PDE4 inhibitors for its anti-inflammatory effects. It has been investigated for its applications to the treatment of conditions such as asthma, dermatitis, rheumatoid arthritis. Emesis is the most commonly cited side effect of piclamilast.

Indole-3-carbinol (I3C), a common phytochemical in cruciferous vegetables, and its condensation product, 3,3'-diindolylmethane (DIM) exert several biological activities on cellular and molecular levels, which contribute to their well-recognized chemoprevention potential. ndole-3-carbinol is used for prevention of breast cancer, colon cancer, and other types of cancer. The National Institutes of Health (NIH) has reviewed indole-3-carbinol as a possible cancer preventive agent and is now sponsoring clinical research for breast cancer prevention. Indole-3-carbinol is also used for fibromyalgia, tumors inside the voice box (laryngeal papillomatosis) caused by a virus, tumors inside the respiratory tract (respiratory papillomatosis) caused by a virus, abnormal cell growth in the cervix (cervical dysplasia), and systemic lupus erythematosus (SLE). Indole-3-carbinol scavenges free radicals and induces various hepatic cytochrome P450 monooxygenases. Specifically, this agent induces the hepatic monooxygenase cytochrome P4501A1 (CYP1A1), resulting in increased 2-hydroxylation of estrogens and increased production of the chemoprotective estrogen 2-hydroxyestrone. Accumulating evidence indicates that the antitumor activity of indole-3- carbinol is attributable to its ability to interfere with multiple oncogenic signaling pathways governing cell cycle progression, survival, invasion, and other aggressive phenotypes of cancer cells. Reported signaling targets of indole-3- carbinol in various cancer cell lines include EGFR/Src, Akt/NF-B, stress responses, elastase, and Rho kinase. Moreover, indole-3-carbinol functions as a negative regulator of estrogen action in hormonesensitive cancer cells through the inhibition of estrogen receptor (ER)-alpha signaling and/or induction of cytochrome P-450-mediated estrogen metabolism, suggesting its clinical use in hormone-sensitive cancers.