SEN12333 is a alpha7 nicotinic acetylcholine receptor agonist for treatment of neurodegenerative and cognitive disorders.

N-Methylspiperone (NMSP) is a derivate of spiperone and high-affinity D2/3 dopamine and 5-HT2A serotonin receptor antagonist. In the biodistribution studies in rodents, there was a high accumulation of radioactivity in the liver, lung, and kidneys, whereas the brain radioactivity was not as high N-Methylspiperone is used to study the dopamine and serotonin neurotransmitter systems. Labeled with the radioisotope carbon-11, it can be used for positron emission tomography (PET). [11C] N-Methylspiperone PET is useful for objective monitoring of D2and 5-HT2A receptor occupancy and density in patients being treated with antipsychotic drugs.

The investigational psychopharmacologic drug candidate CP 615003 (NGD 91-3) is a potent subtype-selective partial agonist at the GABA-A receptor complex. It was designed to be fast acting without causing the sedation, memory impairment, addiction or potentiation of effects of alcohol associated with conventional anti-anxiety medication. Tissue distribution studies conducted during early clinical development of CP 615003 suggested limited brain penetration. In the Phase II clinical study, subjects tested at the high dose of NGD 91-3 showed a trend toward efficacy that did not achieve statistical significance.

AZ-1080 (AZD-1080) is an inhibitor of GSK-beta which was developed by AstraZeneca and initially tested in patients with Alzheimer’s disease (phase I). The drug was discontinued for the aforementioned condition, but now it is being investigated as a potential therapy for ovarina cancer and emdometrial carcinoma (basic research).

C16 (PKRi) is a selective inhibitor of the enzyme double-stranded RNA-dependent protein kinase (PKR). PKRi prevents striatal neurodegeneration and improves behavioral outcomes in a chemically induced mouse model of Huntington's disease, the efffect mediated by off-target inhibition of CDKs. PKRi restored memory deficit in a mouse model of Alzheimer's disease. In a mouse model of colon-26 adenocarcinoma, treatment with C16 lead to a significantly higher level of blood glucose and lower level of serum triglyceride compared with placebo group, which indicates potential use for alleviation of cachexia.

Chelerythrine is a kind of benzo[c] phenanthridine alkaloids, which is widely found in plant of Fumariaceae, Papaveraceae, Ranunculaceae and Rutaceae families. Chelerythrine is a potent and specific inhibitor of protein kinase C. In addition chelerythrine inhibits pro-survival protein Bcl(XL) thereby inducing apoptosis. It exerts antitumor properties.

PD-169316 is a selective inhibitor of p38 MAPK. It inhibits p38 MAPK with an IC50 of 89 nM. PD169316, inhibits transforming growth factor beta-induced Smad signaling in human ovarian cancer cells. In an amyloid β (Aβ) rat model of Alzheimer's disease it was demonstrated that caspase-3 and Bax/Bcl-2 ratio, two marks of apoptosis, were significantly decreased in the rats pre-treated with PD169316 intracerebroventricularly.This study suggested the potential neuroprotective role of PD 169316 against the neuronal toxicity induced by Aβ.

SB-202190 is a potent inhibitor of MAPK14 and MAPK11. It has been investigated in a number of preliminary cell-based studies including several cancer models. SB-202190 has been shown to be a UVB protectant; SB-202190 strongly inhibits UVB induced COX-2 protein expression in HaCaT cells and markedly inhibits UVB induced cox-2 mRNA. SB-202190 induces apoptosis through activation of CPP32-like caspases. SB-202190 has been studied in animal models of the Renal Fibrosis and Pemphigus Vulgaris. It should be noted that in vivo use is most effective (at least for renal fibrosis) when SB-202190 is conjugated to lysozyme using a universal linkage system.

AS601245 (1,3-benzothiazol-2-yl (2-{[2-(3-pyridinyl) ethyl] amino}-4 pyrimidinyl) acetonitrile) is a potent and selective JNK inhibitor developed by Applied Research Systems ARS Holding as promising neuroprotective agent. In vitro AS601245 is a potent and cell permeable ATP competitive JNK inhibitor, which has been shown to inhibit the JNK signaling pathway, promotes cell survival after cerebral ischemia. AS601245 and clofibrate have a synergistic effect in inducing cell responses and in affecting the gene expression profile in CaCo-2 colon cancer cells. AS601245 is a new potent adenosine triphosphate-competitive JNK inhibitor, provides significant protection against the delayed loss of hippocampal CA1 neurons in a gerbil model of transient global ischemia and is also neuroprotective in rats after focal cerebral ischemia. The ischemia-induced phospho-c-Jun expression is attenuated by AS601245, providing a mechanism through which AS601245 blocks the loss of neuronal cells.

AS-605240 is a potent and selective phosphoinositide 3-kinase (PI3K) gamma inhibitor. It selectively inhibits PI3Kgamma enzymatic activity as well as PI3Kgamma-mediated signaling and chemotaxis in vitro and in vivo. It also has peripheral activity versus other PI3K isoforms. AS-605240 did not progress to clinical development although it had been described as a development candidate.