Cizolirtine is a potent analgesic in mice and rats, with an efficacy superior to that of aspirin and other nonsteroid anti-inflammatory drugs. Recent studies have shown that the analgesic effect of cizolirtine could be related, at least partially, to an inhibition of spinal substance P and calcitonin gene-related peptide release. Cizolirtine has been in clinical trials for the treatment of pain and overactive bladder. Reported adverse events are: dry mouth, dizziness, nausea, vomiting, blurred vision.

Ufiprazole (Omeprazole sulfide) is a metabolite of Omeprazole, which is a proton pump inhibitor. Omeprazole sulfide has been shown to be a direct-acting inhibitor of CYP2C19 in pooled human liver microsomes. Ufiprazole is also a weak BRS-3 agonist.

Irosustat is a first-generation, orally active, irreversible steroid sulfatase inhibitor. It did not stimulate the growth of estrogen-sensitive MCF-7 breast cells in vitro. Irosustat was in phase II clinical trials for the treatment of breast cancer and endometrial cancer and phase I clinical trial for the treatment of prostate cancer. However, this research has been discontinued.

Alisertib (MLN8237) is an orally available selective aurora A kinase inhibitor developed by Takeda. Alisertib inhibited AAK over ABK with a selectivity of more than 200-fold in cells and produced a dose-dependent decrease in bipolar and aligned chromosomes in the HCT-116 xenograft model, a phenotype consistent with AAK inhibition. Alisertib inhibited proliferation of human tumor cell lines in vitro and produced tumor growth inhibition in solid tumor xenograft models and regressions in in vivo lymphoma models. It is currently in phase II clinical trials for acute myeloid leukaemia; B cell lymphoma; brain cancer; mesothelioma; prostate cancer; small cell lung cancer.

Fenclonine, also known as p-chlorophenylalanine, is an inhibitor of tryptophan hydroxylase, the enzyme that plays a rate-limiting role in the biosynthesis of serotonin. Fenclonine was studied for the treatment of carcinoid syndrome, but the psychological side effects, prevented for the further development for this use.

Finrozole is a nonsteroidal competitive aromatase inhibitor that is being evaluated in Phase II trials for the treatment of lower urinary tract symptoms associated with reduced androgen/estrogen ratio in aging males associated with benign prostatic hyperplasia. But this research was discontinued in 2005. In dimethylbenzanthracene-induced rat mammary carcinoma model, Finrozole causes regression of more than 80% of the established tumors. The hormone-dependent mammary tumors are inhibited to a level seen in ovariectomised animals.

CGI-1842 (also known as JI-101) is an oral multi-kinase inhibitor that targets vascular endothelial growth factor receptor type 2 (VEGFR-2), platelet derived growth factor receptor β (PDGFR-β), and ephrin type-B receptor 4 that has been used in trials studying the treatment of Cancer, Colon Cancer, Neuroendocrine, Ovarian Cancer, and Advanced Solid Tumors. By targeting multiple angiogenesis signaling pathways in tumor vessel beds, CGI-1842 has the potential to inhibit multiple stages of tumor angiogenesis and thus enhance anti-tumor efficacy. In preclinical models, CGI-1842 induced concentration-dependent blocking of both EphB4- and VEGF-stimulated signaling pathways and has shown excellent antitumor activity. CGI-1842 is well tolerated in cancer patients and has shown impressive activity in Phase I clinical trials.

Dinaciclib (SCH 727965) is a small molecule inhibitor of cyclin-dependent kinases. Dinaciclib demostrates potent and selective inhibition of CDK2, CDK5, CDK1, and CDK9 activity. Dinaciclib inhibits cell cycle progression and proliferation in various tumor cell lines in vitro. Dinaciclib is a product of a drug discovery collaboration between Pharmacopeia (later Ligand Pharmaceuticals) and Schering-Plough (later Merck & Co.) that began in 1998. Dinaciclib showed promising effect in treating haematological malignancies and solid tumors.

Afuresertib (GSK2110183 ) is an orally bioavailable inhibitor of the serine/threonine protein kinase Akt (protein kinase B) with potential antineoplastic activity. Afuresertib binds to and inhibits the activity of Akt, which may result in inhibition of the PI3K/Akt signaling pathway and tumor cell proliferation and the induction of tumor cell apoptosis. Activation of the PI3K/Akt signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K/Akt signaling may contribute to tumor resistance to a variety of antineoplastic agents. Preclinically, AKT inhibition by afuresertib can reverse platinum resistance in ovarian cancer cell lines isolated from patients with platinum-resistant ovarian cancer. Afuresertib is well tolerated and demonstrates clinical activity as monotherapy in heavily pretreated MM patients. Is in phase II clinical trials for Chronic lymphocytic leukaemia; Haematological malignancies; Histiocytosis.