PND-1186, also known as SR-2156 and VS-4718, is a potent FAK inhibitor with a 50% inhibitory concentration (IC50) of 1.5 nM in vitro. PND-1186 has an IC50 of ~100 nM in breast carcinoma cells. PND-1186 is currently being evaluated in a Phase 1 trial in patients with advanced solid tumors. In addition, an ongoing collaboration with Wash U is evaluating PND-1186 in combination with gemcitabine and Abraxane in 1st line pancreatic cancer.

Entospletinib (GS-9973) is an adenosine triphosphate competitive inhibitor of Syk that disrupts kinase activity, which is currently in clinical trials for multiple B-cell malignancies. The most common treatment-emergent serious adverse events included dyspnea, pneumonia, febrile neutropenia, dehydration, and pyrexia.

Entospletinib (GS-9973) is an adenosine triphosphate competitive inhibitor of Syk that disrupts kinase activity, which is currently in clinical trials for multiple B-cell malignancies. The most common treatment-emergent serious adverse events included dyspnea, pneumonia, febrile neutropenia, dehydration, and pyrexia.

Omtriptolide (previously known as PG490-88 or F60008), an immunosuppressant that has been shown to be the safe and potent antitumor agent and it has been approved entry into Phase I clinical trial for the treatment of prostate cancer in the USA. In addition, the drug is participating in phase I clinical trial for the treatment of myeloid leukemia. Experiments on animals have shown omtriptolide was highly effective in the prevention of murine graft-versus-host disease (GVHD). The immunosuppressive effect of the drug was mediated by inhibition of alloreactive T cell expansion through interleukin-2 production. However, this study was discontinued. Recently published article has shown omtriptolide possesses the potential as a prophylactic agent to prevent ischemia/reperfusion (I/R)-induced lung injury.

MK-2206 is an oral selective allosteric inhibitor of Akt that targets all three isoforms of human Akt (Akt-1, Akt-2 and Akt-3). In a phase I study of solid tumors, MK-2206 demonstrated evidence of target modulation and anti-proliferative activity as a single agent and in combination with other agents. Current ongoing trials of MK-2206 include monotherapy and combination therapy in breast cancer, colorectal cancer, haematological malignancies, non-small cell lung cancer and other. Detected treatment-related adverse event are: rash, fatigue, hyperglycemia.

Idalopirdine (Lu AE58054) is a Serotonin 6 receptor (5-HT6) antagonist. Idalopirdine exrets good oral bioavailability and robust efficacy in a rat model of cognitive impairment in schizophrenia. In rats idalopirdine potentiates the effects of acetylcholinesterase inhibitor donepezil on two pharmacodynamic biomarkers associated with cognition, i.e. neuronal oscillations and extracellular ACh levels in the hippocampus. Such potentiation could contribute to the procognitive effects of idalopirdine observed in donepezil-treated Alzheimer's disease patients. The compound is being developed by Lundbeck as an adjunctive therapy with acetylcholinesterase inhibitor donepezil, and is in phase III development for the treatment of Alzheimer's disease in multiple countries worldwide. A phase II trial for the treatment of cognitive impairment associated with schizophrenia was conducted; however no recent reports of development for idalopirdine have been identified.

ARN-810 (GDC-0810) is a novel, orally bioavailable, estrogen receptor antagonist that induces proteasomal estrogen receptor degradation in breast cancer cell lines at picomolar concentrations and tumor regression in tamoxifen-sensitive and resistant BC xenograft models. Results from a first-in-human phase I/IIa study of ARN-810 indicate that it is tolerable and may benefit some postmenopausal women with advanced estrogen receptor-positive breast cancer. Development of ARN-810 was discontinued.

INT-131, a novel, non-thiazolidinedione (TZD), selective peroxisome proliferator-activated receptor (PPAR) gamma modulator and partial agonist, which was investigated in phase II of clinical trial for the treatment of type 2 diabetes mellitus (non-insulin dependent diabetes) and Multiple Sclerosis, Relapsing Remitting. The concept of selective modulation involves targeting and activating specific genes to minimize side effects while maintaining therapeutic benefits. In vitro, INT-131 attenuated adipogenic properties, indicating moderate PPAR gamma activation/cofactor recruitment compared with the full agonistic properties of TZD compounds.

Vesatolimod, also known as GS-9620, is being developed in clinical studies for the treatment of chronic hepatitis B viral (HBV) infection, with the goal of inducing a liver-targeted antiviral effect without inducing the adverse effects associated with current systemic interferon-α (IFN-α) therapies. It is demonstrate interferon-stimulated gene induction without detectable serum interferon at low oral doses. GS-9620 is a potent and oral agonist of Toll-like receptor-7, a pattern-recognition receptor whose activation results in innate and adaptive immune stimulation

Dofequidar (MS-209), a quinolone-derived sphingomyelin synthase inhibitor that blocks P-glycoprotein and multidrug resistance-associated protein-1, is under development by Schering for the potential treatment of multidrug resistant tumors. MS-209 had been in phase III clinical trials for the treatment of breast cancer and non-small lung cancer. But this research was discontinued in 2004. Detected adverse events are: nausea, vomiting, leukopenia, neutropenia, anorexia, constipation.