Briciclib (also known as ON-013105 and ON-014185) has the potential of targeting and inhibition of eukaryotic translation initiation factor 4E (eIF4E) for solid cancers. eIF4E is a proto-oncogene that promotes translation of several genes essential for cellular proliferation (cyclin D1, c-Myc, mTOR), survival (Akt), angiogenesis (VEGF), and metastasis (MMP9). Overexpression of eIF4E has been observed in almost all major groups of cancers and has been shown to induce increased expression of cyclin D1 and c-Myc). An intravenous formulation of briciclib was being investigated in the Phase 1 clinical trial. The purpose of the study was to determine the highest dose of briciclib that could be given safely in patients with relapsed/refractory Lymphoma or B-cell Acute Lymphocytic Leukemia (Philadelphia chromosome negative). However, this study was terminated because of the lack of available clinical drug supply. In addition, briciclib was also involved in phase I clinical trials with advanced cancer and solid tumors, to determine the highest dose that can be safely given.

Naquotinib (ASP8273) is an orally available, irreversible, mutant-selective, epidermal growth factor receptor (EGFR) inhibitor, with potential antineoplastic activity. Naquotinib was found by mass spectrometry to covalently bind to a mutant EGFR (L858R/ T790M) via cysteine residue 797 in the kinase domain of EGFR with long-lasting inhibition of EGFR phosphorylation for 24 h. In the NSCLC cell lines harboring the above EGFR mutations, Naquotinib had IC50 values of 8-33 nM toward EGFR mutants, more potently than that of WT EGFR (IC50 value of 230 nM). In mouse xenograft models, Naquotinib induced complete regression of the tumors after 14 days of treatment. ASP8273 even showed activity in mutant EGFR cell line which is resistant to other EGFR TKIs. Naquotinib is in phase III clinical trials for the oral treatment of EGFR mutated non-small cell lung cancer (NSCLC).

2-Iminobiotin (2-IB) is a cyclic guanidino analog of biotin (Vitamin B7) and combined neuronal and inducible (but not endothelial) nitric oxide synthase inhibitor that has been demonstrated to improve neuroprotection in animal models of hypoxic-ischemic Brain Injury. While the exact mechanism of action has yet to be defined, 2-Iminobiotin potentially protects against hypoxic-ischemic brain damage by preventing nitric oxide or peroxynitrite-induced mitochondrial damage. In preclinical models, 2-Iminobiotin provides gender-specific neuroprotection against hypoxia-ischemia in neonatal rats by a NO-independent mechanism.

BMS-833923 was discovered by Exelixis and was out-licensed to Bristol-Myers Squibb. BMS-833923 is an orally bioavailable Smoothened antagonist. BMS-833923 reduces hedgehog pathway activity, decreases cell proliferation and induces apoptosis via the intrinsic pathway in esophageal adenocarcinoma (EAC) cell lines. BMS-833923 dose-dependently affects canonical and prostate hedgehog signature gene transcription in vitro. BMS-833923 is in phase II clinical trials for the treatment of chronic myeloid leukaemia.

NS-3728 (Endovion) is an orally active chloride channel blocker for the treatment of cancer. Endovion was originally discovered by NeuroSearch. In August 2004, NeuroSearch entered into a collaboration with TopoTarget to develop its compound Endovion, an orally active chloride channel blocker for the treatment of cancer. Endovion blocks a certain subtype of chloride ion channels important for cell division, cell migration and the formation of new blood vessels (angiogenesis). Endovion has shown efficacy in preclinical cancer models. The compound has completed Phase I clinical trials in 92 subjects. Endovion had been in phase I clinical trials for the treatment of sickle cell anemia and solid tumours. TopoTarget has discontinued development of Endovion for use in glioblastoma. It was discontinued as supplementary preclinical trials did not support its activity as an anticancer agent. Early studies as an anti sickling agent were discontinued due to higher costs than first estimated for the clinical programme.