Talopram (Lu 3-010) is a selective inhibitor norepinephrine transporter belonging to the antidepressants of the thymoleptic group.

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).

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.

Roniciclib (BAY1000394) is a pan-cyclin-dependent kinase inhibitor that has been developed for treatment in small cell lung carcinoma and solid tumors. Roniciclib targets certain key proteins that are essential for the survival of cancer cells, resulting in decreased tumor growth. Phase I studies to evaluate the safety, tolerability and pharmacokinetics of roniciclib have been completed successfully. In phase II studies, roniciclib was found to be well tolerated and showed promising efficacy when combined with chemotherapy in small cell lung carcinoma patients. However, due to an observed safety signal (treatment-emergent adverse events) in one phase II study, other clinical trials have been discontinued and further development of roniciclib was terminated.

Amgen is developing AMG-900, an orally active, small molecule aurora kinase A, B and C inhibitor for the treatment of solid tumours and haematological malignancies. In tumor cells, AMG-900 inhibited autophosphorylation of aurora-A and -B as well as phosphorylation of histone H3 on Ser(10), a proximal substrate of aurora-B. The predominant cellular response of tumor cells to AMG-900 treatment was aborted cell division without a prolonged mitotic arrest, which ultimately resulted in cell death. AMG-900 inhibited the proliferation of 26 tumor cell lines, including cell lines resistant to the antimitotic drug paclitaxel and to other aurora kinase inhibitors (AZD1152, MK-0457, and PHA-739358), at low nanomolar concentrations. Furthermore, AMG-900 was active in an AZD1152-resistant HCT116 variant cell line that harbors an aurora-B mutation (W221L). Oral administration of AMG-900 blocked the phosphorylation of histone H3 in a dose-dependent manner and significantly inhibited the growth of HCT116 tumor xenografts. Importantly, AMG-900 was broadly active in multiple xenograft models, including 3 multidrug-resistant xenograft models, representing 5 tumor types. AMG-900 has entered clinical evaluation in adult patients with advanced cancers and has the potential to treat tumors refractory to anticancer drugs such as the taxanes.

Lixivaptan is an orally-active, vasopressin 2 receptor antagonist. It is indicated for the treatment of symptomatic hypervolemic and euvolemic hyponatremia, associated with heart failure (HF) and syndrome of inappropriate antidiuretic hormone (SIADH). Adverse events likely to be result of the pharmacologic action of lixivaptan are: constipation, dry mouth, dizziness, insomnia. Grapefruit juice significantly increased the extent of lixivaptan absorption as compared to lixivaptan administered under fasted conditions but not under fed conditions. Lixivaptan Cmax and AUC∞ increased by 2.4-fold and 3.2-fold, respectively, when lixivaptan was administered with ketoconazole (the same in case of Simvastatin).

FENPIPALONE is an oxazolidinone derivative with central nervous system depressant and antiinflammatory activity in animal models. However, FENPIPALONE did not demonstrate any usefulness for severely ill chronic schizophrenic patients.

Endoxifen, also known as N-desmethyl-4-hydroxytamoxifen, is active metabolites of tamoxifen. This metabolite exhibits a 100-fold higher binding affinity to the estrogen receptor (ER) and are more effective in suppressing cell proliferation than tamoxifen. In humans, the conversion from tamoxifen to endoxifen is predominant. Endoxifenis is an orally active, selective estrogen receptor modulator (SERM) that was developed for the treatment of estrogen receptor-positive breast cancer. In addition, this drug possesses antimanic properties, what can be used in the treatment of patients with bipolar I disorder (BPD I).

Eleclazine (formerly known as GS-6615) is a dihydrobenzoxazepinone selective cardiac late sodium current inhibitor. Gilead Sciences is developing eleclazine as an oral treatment for long QT syndrome, hypertrophic cardiomyopathy, ischaemic heart disease, and Ventricular arrhythmias.