Filanesib is a highly selective, targeted KSP inhibitor with a mechanism of action distinct from currently available myeloma therapies such as immunomodulatory drugs (IMiDs®) and proteasome inhibitors. Across multiple studies, filanesib has demonstrated activity in heavily pretreated multiple myeloma patients, with a consistent safety profile including no drug-induced peripheral neuropathy and limited non-hematologic toxicity. Adverse events are generally limited to transient, non-cumulative and predominantly asymptomatic myelosuppression (decreases in blood counts) when supportive measures are used. Alpha 1-acid glycoprotein (AAG), a plasma protein, is a potential patient selection marker for filanesib. AAG is undergoing further investigation in clinical trials and could represent the first patient selection marker for a myeloma therapy. Filanesib is in Phase II for Multiple myeloma treatment.

Rabusertib is a Chk1 kinase inhibitor which was developed by ICOS for the treatment of cancer. The drug was tested in phase II of clinical trials for pancreatic cancer and non small cell lung carcinoma, but its development was discontinued. Now the drug is undergoing phase I trial in Japanese patients with solid tumors.

Pilaralisib (XL147, SAR245408) is a potent and highly selective inhibitor of class I phosphatidylinositol 3-kinase (PI3K) (α, β, γ, and δ). In cellular assays, XL147 inhibits the formation of PIP3 in the membrane, and inhibits phosphorylation of AKT, p70S6K, and S6 in multiple tumor cell lines with diverse genetic alterations affecting the PI3K pathway. In a panel of tumor cell lines, XL147 inhibits proliferation with a wide range of potencies, with evidence of an impact of genotype on sensitivity. Repeat-dose administration of XL147 results in significant tumor growth inhibition in multiple human xenograft models in nude mice. Pilaralisib, was being developed by Exelixis and its licensee, Sanofi (formerly sanofi-aventis), for the treatment of solid tumours. However, the product was not listed on Sanofi's early stage pipeline as of end of July 2015 and there have been no recent reports on development identified.

Enciprazine also known as WY-48624 or, D-3112 is a GABA A receptor agonist which was in the phase III of clinical trial for the treatment of anxiety disorders. Enciprazine was well tolerated, with low levels of sedative and asthenic side effects reported. However, research was discontinued.

Nefiracetam is a cyclic derivative of gamma-aminobutyric acid (GABA). It is thought to act by normalising dysfunctional acetylcholine, GABA and possibly monoamine neurotransmitter systems, but it may also facilitate N/L-type calcium channel opening. Nefiracetam has received attention as a treatment for seizures, depression, and dementia. Nefiracetam was found to be extremely testicular toxic in both rats and dogs; it was found to significantly decrease the levels of testicular testosterone leading to atrophy and malformation of sperm.

AZD1775 selectively targets and inhibits WEE1, a tyrosine kinase that phosphorylates cyclin-dependent kinase 1 (CDK1, CDC2) to inactivate the CDC2/cyclin B complex. Inhibition of WEE1 activity prevents the phosphorylation of CDC2 and impairs the G2 DNA damage checkpoint. This may lead to apoptosis upon treatment with DNA damaging chemotherapeutic agents. Current ongoing trials of AZD1775 include monotherapy and combination therapy with certain DNA damaging agents in solid tumors, ovarian tumors, gynaecological cancer, non-small cell lung cancer. AZD1775 is genotoxic, which is considered to be a result of its mechanism of action. Common serious adverse events (with chemotherapy) include: febrile neutropenia, neutropenia, thrombocytopenia.

Pelitinib (EKB-569) is a 3-cyanoquinoline pan-ErbB tyrosine kinase inhibitor with potential antineoplastic activity. Pelitinib irreversibly binds covalently to epidermal growth factor receptors, thereby inhibiting receptor phosphorylation and signal transduction and resulting in apoptosis and suppression of proliferation in tumor cells that overexpress these receptors. Pelitinib had been in phase II clinical trials for the treatment of non-small cell lung cancer and colorectal cancer. Treatment-emergent adverse events were diarrhea, abdominal pain, gastrointestinal carcinoma, intestinal obstruction and vomiting.

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.

BMS 599626 is a selective and efficacious inhibitor of HER1 and HER2 with IC50 of 20 nM and 30 nM. BMS-599626 is identified as an ATP-competitive inhibitor for HER1 and as an ATP-noncompetitive inhibitor for HER2. BMS-599626 inhibits the proliferation of tumor cells expressing high levels of HER1 and/or HER2, including Sal2, BT474, N87, KPL-4, HCC202, HCC1954, HCC1419, AU565, ZR-75-30, MDA-MB-175, GEO, and PC9 cells. In a phase I trial of solid tumour patients receiving BMS 599626 no doselimiting toxicities were observed during the first cycle. Grade 1 or 2 drugrelated effects were reported and included diarrhoea, nausea, vomiting, rash, fatigue, musculoskeletal pain/cramp and cough. BristolMyers Squibb discontinued development of BMS 599626 for cancer in July 2015

Sanguinarine is an extract of the bloodroot plant Sanguinaria canadensis, a member of the poppy family. It is an inhibitor of protein phosphatases PP1, PP2C and PP2B in vitro. Also inhibits mitogen-activated protein kinase phosphatase-1 (MKP-1) and other enzymes. Sanguinarine exerts a protective effect in cerebral ischemia, and this effect is associated with its anti-inflammatory and anti-apoptotic properties. It was clinically tested as an agent against gingivitis and tooth plaques.