CP 316819 is the selective glycogen phosphorylase inhibitor. CP 316819 has been extensively evaluated as antihyperglycemic agents for type 2 diabetes because of its potential to limit hepatic production of glucose from glycogen without inducing hypoglycemia. Under low glucose conditions, CP 316819 facilitates glycogen utilization in the brain, prevents neuronal cell death and maintains brain electrical currents.

PNU-282987 is a potent and selective a7 nAChR agonist. This compound showed high affinity for the rat a7 nAChR (Ki = 26 nM) and activity at the a7–5-HT3 chimera (EC50 = 128 nM). In addition, PNU-282987 was found to be inactive at all tested monoamine, muscarine, glutamate, and GABA receptors at 1 uM concentration, except 5-HT3 receptors (Ki = 930 nM). The highly selective and potent a7 nAChR agonist PNU-282987 enhances GABAergic synaptic activity in the hippocampus in vitro, and reverses amphetamine induced auditory gating deficit in anesthetized rats. In addition, PNU-282987 improves the inherent gating deficit observed in a subset of rats and enhances amphetamine induced hippocampal activity. These results support the concept that a7 nAChR agonists represent a novel, potential pharmacotherapy in treatment of schizophrenia. It also has being shown that acute lung injury is reduced by PNU-282987 through changes in the macrophage profile.

PF-670462 is a selective inhibitor of the δ- and ε-isoforms of casein kinase I, with IC50 values of 7.7 and 14 nM respectively, and >30 selectivity relative to 42 other kinases tested. Casein kinase Iε phosphorylates PER proteins, which are involved in setting the period of the circadian pacemaker or clock. PF-670462 is potent (IC50 7.7 nM) and effective in vivo (i.e. it induces profound phase delays in circadian periodicity). PF-670462 has being shown to have an ability to induce phase delays in circadian rhythms in rats, in which it is rapidly metabolized, and in monkeys. A potential pharmacological use of the compounds like PF-670462 could be for therapy of cognitive deficits in shift workers, mood changes in bipolar disorders, and phase advances in the sleep–wake cycle in elderly people. It has also being shown that Inhibition of the casein-kinase-1-ε/δ/ with PF-670462 prevents relapse-like alcohol drinking in rats, suggesting that CK1 inhibitors may be candidates for drug treatment development for alcoholism.

PF-4778574 is a potent AMPA receptor positive allosteric modulator (PAM) that has been shown to enhance cognition in animal models.Displacement studies using [3 H]PF-04725379 in rat cortical tissue determined a Ki of 85 nM for PF-4778574. The AMPAR potentiator PF-4778574 was characterized in a series of in vitro assays and acute-dose animal studies evaluating AMPAR-mediated mechanism, safety, and nootropism. Potentiator-induced animal effects were likely purely AMPAR-dependent since PF-4778574 (10 uM) only affected the dopamine transporter (IC50 of 910 nM) in a broad human-based receptor/enzyme selectivity panel.

The small molecule PF-429242 was developed as a hypolipidemic agent based on high throughput screening in a Pfizer compound library. PF-429242 is a competitive inhibitor of sterol regulatory element-binding protein (SREBP) site 1 protease (IC50 = 0.175 uM). It is selective for site 1 protease against a panel of serine proteases. PF-429242 inhibits rate of cholesterol synthesis in CHO cells (IC50 = 0.53 uM). PF-429242 inhibits the activity of S1P reversibly and competitively and suppresses the expression level of SREBP target genes, consequently decreasing cellular lipid levels. It has been shown that PF-429242 suppresses hepatic SREBP target genes and inhibits cholesterol and fatty acid synthesis in a mouse model. It also has been reported that PF-429242 suppresses viral replication in cells infected with hepatitis C virus (HCV), Lassa virus, lymphocytic choriomeningitis virus, New World arenaviruses and Dengue virus.

PF-3845 is a selective covalent inhibitor of fatty acid amide hydrolase. It results in increased levels of anandamide and results in cannabinoid receptor-based effects. PF-3845 demonstrated cannabinoid receptor-dependent antinociceptive effects in models of inflammatory and neuropathic pain. In mouse model PF-3845 attenuated withdrawal from morphine dependence. PF3845 reversed traumatic brain injury (TBI)-induced impairments in fine motor movement, hippocampus dependent working memory and anxiety-like behavior in a tramatic brain injury model.

PF-03716556 is a novel, potent, and selective acid pump antagonist for the treatment of gastroesophageal reflux disease. PF-03716556 inhibits the porcine, canine, and human recombinant gastric H+,K+-ATPase in a competitive manner without any biologically relevant activity against other tested receptors, ion channels, and enzymes, including the Na+,K+-ATPase. PF-03716556 inhibits gastric acid secretion in a dose-dependent manner in Ghosh-Schild rats and Heidenhain pouch dogs, producing full efficacy on treatment day 1. PF-03716556 is used for the treatment of gastroesophageal reflux disease.

A novel pyrido[2,3-d]pyrimidine derivative, PD-180970, has been shown to potently inhibit Bcr-Abl and induce apoptosis in Bcr-Abl-expressing leukemic cells. PD-180970 is active against several Bcr-Abl mutations that are resistant to imatinib and support the notion that developing additional Abl kinase inhibitors would be useful as a treatment strategy for chronic myelogenous leukemia. PD-180970 is also an inhibitor of Src, and KIT.

PQ-10 belongs to the same class as the PDE10 inhibitor papaverine, but IC50 literature suggests that is about 5 times more potent then papaverine, yet still about 10 times less potent the known PDE10 inhibitors TP- 10 and MP-10. Preclinical development is ongoing in USA for the treatment of psychotic disorders.

CP-465022 is a potent, and selective noncompetitive AMPA receptor antagonist. It provides neuroprotective efficacy after cerebral ischemia on the basis of the activity in experimental ischemia models. CP-465022 inhibits AMPA receptor-mediated whole cell currents in rat cortical neurons in primary culture with an IC50 value of 30 nM but only weakly inhibits NMDA, g-aminobutyric acid, or kainate receptor-mediated currents. CP-465022 binds to the AMPA receptor with high affinity (IC50 = 36 nM) and displays potent anticonvulsant activity. The compound does not discriminate among AMPA receptors composed of different homomeric or heteromeric subunit combinations. Furthermore, CP-465022 inhibits AMPA receptor activity in a noncompetitive manner that is neither voltage- nor use-dependent. When administered to rodents systemically, CP-465022 inhibits AMPA receptor-mediated synaptic transmission and chemically induced seizures.