PF-05175157 exhibited good potencies against the two isoforms of the Acetyl-CoA carboxylase enzyme (ACC1 and ACC2) from human and rat. PF-05175157 has undergone multiple clinical trials in healthy volunteers and for the treatment of diabetes mellitus. PF-05175157 was in the phase II when the development was discontinued due to safety concerns. Among potential barriers for the use of ACC inhibitors in humans include concerns of increased risk of myocardial injury following an ischemic event. PF-05175157 reduced the multiplication of West Nile virus (WNV), dengue virus (DENV), and Zika virus (ZIKV) in cultured cells, which is compatible with the predicted broad spectrum of host targeting antivirals. PF-05175157 reduced the peak of viremia in WNV-infected mice, supporting that ACC is a valuable target for antiviral intervention. PF05175157 also reduced the viral burden in the kidney of infected mice.

PF-02413873 is a selective nonsteroidal progesterone receptor (PR) antagonist. PF-02413873 is turned over by recombinant human P450s, with CYP3A4 displaying the highest turnover of those enzymes tested. PF-02413873 possessed low oral clearance in human with a pharmacokinetic profile consistent with a once-daily dosing schedule. The pharmacological mode of action of PF-02413873 seems to differ from the founding member of the class of steroidal PR antagonists RU-486. Exposure-effect data from studies in the cynomolgus macaque, however, demonstrated that PF-02413873 reduced endometrial functionalis thickness to a comparable degree to RU-486 and this effect was accompanied by a decrease in proliferation rate for both RU-486 and high-dose PF-02413873. PF-02413873blocked the follicular phase increase in endometrial thickness, the midcycle luteinizing hormone surge, and elevation in estradiol in a dose-dependent fashion compared with placebo. PF-02413873 had been in phase I clinical trial for the treatment of endometriosis. However, this development was discontinued.

PF-04217903 is a triazolopyrazine inhibitor of c-MET that displays anticancer chemotherapeutic and anti-metastatic activities. PF-04217903 inhibits cell proliferation, invasion, and migration as well as tumor growth in various cancer models. In animal models of pancreatic neuroendocrine tumors, this compound prevents lymph node metastasis. PF-04217903 had been in phase I clinical trials by Pfizer for the treatment of solid tumors. In 2011, the company discontinued the development of the compound.

Pfizer was developing PF-3882845, an orally available nonsteroidal antagonist of the mineralocorticoid receptor, for the treatment of diabetic nephropathies. PF‐03882845 is a highly potent (IC50 = 6.3‐13.4 nM, 10% fetal bovine serum & IC50 = 0.504–1.11 nM, absence of serum) selective orally bioavailable mineralocorticoid receptor antagonist. It is a non‐steroidal pyrazoline, unlike steroidal compounds eplerenone and spironolactone. It does not significantly activate or inhibit human androgen receptor, estrogen receptor alpha, and glucocorticoid receptor. PF‐03882845 has been shown to modestly inhibit the progesterone receptor (PR) yielding a 45‐fold selectivity over PR in a cell‐based functional assay. PF‐03882845 was previously in development for the treatment of diabetic nephropathy — development for this indication was terminated for strategic reasons. An alternative indication of hypertension also was not pursued for strategic reasons.

PF-04691502 is a PI3K/mTOR dual inhibitor. It was tested in phase 2 clinical trials against endometrial cancer and breast cancer, but its development was discontinued due to unacceptable toxicity.

PF-04958242 is an AMPA receptor potentiator for the potential treatment of cognitive deficits in schizophrenia. But recent study revealed that there were no pharmacokinetic interactions between PF-04958242 and ketamine. 'High-impact' AMPAR potentiators like PF-04958242 may have a role in the treatment of the cognitive symptoms, but not the positive or negative symptoms, associated with schizophrenia. In addition, a clinical study was underway to evaluate the effects of PF-049582432 in subjects with age-related hearing loss in the US. PF-04958242 has been classified as glycine transporter (GLYT-1) inhibitor in this study. However, this development was discontinued.

PF-04620110 is an orally active, selective and potent DGAT1 (Acyl-CoA:diacylglycerol acyltransferase 1) inhibitor that inhibits triacylglycerol synthesis in cells and in rodents. PF-04620110 inhibits DGAT-1 with an IC50 of 19 nM and shows high selectivity versus a broad panel of off-target pharmacologic end points. In vivo DGAT-1 inhibition has been demonstrated through reduction of plasma triglyceride levels in rodents at doses of ≥0.1 mg/kg following a lipid challenge. On the basis of this pharmacologic and pharmacokinetic profile, PF-04620110 has been advanced to human clinical studies. PF-4620110 had been in phase I clinical trials by Pfizer for the treatment of type 2 diabetes. But this research was discontinued in 2011.

Defactinib is an oral, investigational drug candidate for the treatment of various solid tumors. Through dual inhibition of FAK and PYK2, defactinib targets key resistance mechanisms in the tumor microenvironment (TME), including limited local immune response, dense stroma, and resident cancer stem cells, that may limit the effectiveness of current and investigational treatments. Treatment-related adverse events are: unconjugated hyperbilirubinemia, fatigue and headache.

PF-00489791 is the novel, selective and long-acting phosphodiesterase type 5 (PDE5) inhibitor. PF-00489791 was safe and generally well tolerated in overt diabetic nephropathy patient population. Most common adverse events were mild in severity and included headache and upper gastrointestinal events. PF-00489791 is the first long-acting PDE5 inhibitor to demonstrate significant reduction of albuminuria when added to standard of care therapy in subjects with type 2 diabetes mellitus and overt diabetic nephropathy. In addition, PF-00489791 causes a clinically meaningful and sustained blood pressure lowering in patients with hypertension.

PF-04447943 is a potent, selective brain penetrant PDE9 inhibitor (Ki of 2.8, 4.5 and 18 nM) for human, rhesus and rat recombinant PDE9 respectively and high selectivity for PDE9 versus PDEs1-8 and 10-11. PF-04447943 was being developed by Pfizer for the treatment of cognitive disorders. PF-04447943 attenuates a scopolamine-induced deficit in a novel rodent attention task. PF-04447943 enhances synaptic plasticity and cognitive function in rodents. PF-04447943 has completed Phase II clinical trials in subjects with mild to moderate AD in 2013 but this research was discontinued. Pfizer completes a phase I trial in Sickle cell anaemia.