PF-04457845 is a fatty acid amide hydrolase 1 inhibitor developed by Pfizer for the treatment of inflammatory and noninflammatory pain disorders. The drug was tested in phase II in patients with osteoarthritis of the knee, but found to have the same effect as placebo. It was also assessed in phase II clinical trial for its effect on marijuana withdrawal and Tourette syndrome.

Pfizer was developing PF-4995274, an orally administered serotonin 4 receptor (5HT-4) agonist for the treatment of Alzheimer's disease. In 2011, the company discontinued the development of the compound.

Pfizer was developing PF-04991532, a potent and selective hepatoselective glucokinase activator. PF-04991532 ameliorates hyperglycemia without causing hepatic steatosis in diabetic rats. F-04991532 reduced plasma glucose concentrations independent of changes in insulin concentrations in a dose-dependent manner both acutely and after 28 days of sub-chronic treatment. PF-04991532 may offer glycemic control without inducing hepatic steatosis supporting the evaluation of tissue specific activators in clinical trials. In 2012, Pfizer discontinued the development of the compound.

PF-04531083 is selective Nav1.8 blocker. It has been investigated for the treatment of chronic pain, heart pain, post-surgical dental pain. However, these trials were discontinued.

PF-03382792 is an oxindole derivative. PF-03382792 is highly potent and selective 5-HT4 partial agonist. It has excellent brain penetration properties. PF-03382792 increased acetylcholine release in the rat prefrontal cortex. It have been reported to reverse learning deficits induced by cholinergic agents. A safety assessment of this compound revealed large therapeutic margins between efficacious concentrations and safety findings. PF-03382792 reached human Phase I clinical trials but future development was discontinued.

PF-03635659 is a potent, very long dissociative half-life (slow off-rate, >1440 min) muscarinic M3 antagonist. Spirometry data from healthy volunteers in phase I clinical studies illustrate that PF-03635659 provides efficacious 24 h bronchodilation from a single inhaled dose, thus confirming the suitability of PF-03635659 as a novel once-daily inhaled muscarinic M3 receptor antagonist for the treatment of chronic obstructive pulmonary disease (COPD). Safety (tachycardia) and toleration (dry mouth) data from the multidose phase I studies indicate an adverse event profile that is at least noninferior to tiotropium bromide. PF-03635659 had been in phase II clinical trial for the treatment of chronic obstructive pulmonary disease.

Pfizer was developing PF-4455242, a selective, short-acting (non-"inactivating") antagonist of the κ-opioid receptor. PF-4455242 was pursued in phase I clinical trial for the treatment of the bipolar disorder and was also investigated as a treatment for depression and substance abuse. In September 2010 Pfizer discontinued the development of the compound.

PF-3758309 was developed as an ATP-competitive inhibitor of PAK4. In cells, PF-3758309 inhibits phosphorylation of the PAK4 substrate GEF-H1 (IC50 = 1.3 nM) and anchorage-independent growth of a panel of tumor cell lines (IC50 = 4.7 nM). PF-3758309 blocks the growth of multiple human tumor xenografts, with a plasma EC50 value of 0.4 nM in the most sensitive model. PF-3758309 is antiproliferative and induces apoptosis in an HCT116 tumor model.

PF-4191834 is a noniron chelating, non-redox inhibitor of the 5-lipoxygenase enzyme (5-LOX) that is being developed as an oral anti-inflammatory therapy for the treatment of asthma. Enzyme assay results demonstrate that PF-4191834 has an improved potency compared with its predecessor CJ-13610 and of zileuton. It was able to reduce pain and inflammation in an adjuvant-induced arthritis model in rats. PF-4191834 offers the potential to test the hypothesis that chronic inhibition of the 5-LOX enzyme will provide maximal efficacy for this target in inflammatory diseases such as asthma, chronic obstructive pulmonary disease, pain, and perhaps lupus. PF-4191834 had been in phase II clinical trial for the treatment of pain. Development was terminated in March 2011.

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.