Voxtalisib (SAR245409, XL765) is an orally available inhibitor of PI3K and the mammalian target of rapamycin (mTOR), which are frequently activated in human tumors and play central roles in tumor cell proliferation. Exelixis discovered Voxtalisib internally and out-licensed the compound to Sanofi. Voxtalisib is being evaluated by Sanofi as a single agent and in multiple combination regimens in a variety of cancer indications. Clinical trials have included a single agent phase 2 trial in Non-Hodgkin’s lymphoma, combination phase 1b/2 trials with temozolomide in patients with glioblastoma, with letrozole in hormone receptor positive breast cancer, with bendamustine and/or rituximab in lymphoma or leukemia, and a phase 1 trial in combination with a MEK inhibitor. Voxtalisib is a highly selective, potent and reversible ATP-competitive inhibitor of pan-Class I PI3K (α, β, γ, and δ) and mTORC1/mTORC2. It is orally active, highly selective over 130 other protein kinases. In cellular assays, XL765 inhibits the formation of PIP3 in the membrane, and inhibits phosphorylation of AKT, p70S6K, and S6 phosphorylation in multiple tumor cell lines with different genetic alterations affecting the PI3K pathway.

AMG 337 is an oral, small molecule, ATP-competitive, highly selective inhibitor of the cell surface enzyme called c-Met, which, when dysregulated, stimulates cancer cell scattering, invasion and protection from apoptosis. AMG 337, currently in Phase 2 development for the treatment of gastric and esophageal adenocarcinoma. In addition, recently was shown, that AMG 337 a promising and novel therapeutic strategy for targeting hepatocellular carcinomas with a dependence on HGF/MET signaling.

AZD-3514 is a down-regulator of androgen receptors. The drug was synthesized by AstraZeneca for the treatment of castrate-resistant prostate cancer and even reached phase I, however, its development was terminated.

CP-866087 is a mu opioid receptor antagonist, discovered by Pfizer. The compound was able to antagonize the effect of morphine in a rodent tail flick assay and produced a dose-dependent decrease in alcohol intake in alcohol-preferring rats. The compound was investigated in clinical trials for the treatment of obesity, alcoholism and female sexual arousal disorder. In the later study, although improvements were seen with CP-866,087 in the key efficacy endpoints, there was no clinical treatment benefit over placebo.

PF-00610355 is ultra long-acting beta 2 adrenergic receptor-agonists that is being developed for ‘once daily’ treatment of asthma. Plasma pharmacokinetics of orally inhaled PF-00610355 are consistent and exhibit a sustained plateau after single/multiple doses, but plasma exposure is reduced in asthmatic patients compared with healthy volunteers. Although substantial increases in heart rate were observed in healthy volunteers, both pharmacokinetic as well as pharmacodynamic differences between healthy volunteers and chronic obstructive pulmonary disease (COPD) patients (the systemic exposure of PF-00610355 is substantially lower in COPD than in healthy volunteers) explain the modest effect of PF-00610355 on heart rate in the patient population. PF-00610355 had been in phase II clinical trials for the treatment of asthma and chronic obstructive pulmonary disease. However, this development was discontinued.

Emilium is an antiarrhythmic agent and cardiac depressant.

Viquidacin (also known as NXL-101), a quinoline antibacterial agent, was studied as a bacterial DNA gyrase and topoisomerase IV inhibitor. Viquidacin showed potent activity against gram-positive bacteria, including methicillin- and fluoroquinolone-resistant strains. The drug participated in phase I clinical trial. Viquidacin achieved homogeneous and potent bactericidal concentrations in human volunteer plasma. However, further, development was discontinued after QT interval prolongation, which was observed in a healthy volunteer.