Darglitazone is a member of the thiazolidinedione class of drugs and an agonist of peroxisome proliferator-activated receptor-γ (PPAR-γ), an orphan member of the nuclear receptor superfamily of transcription factors. It has a variety of insulin-sensitizing effects, such as improving glycemic and lipidemic control, and is used in the treatment of metabolic disorders such as type II diabetes. Darglitazone sodium had been in phase I clinical trials by Pfizer for the treatment of type 2 diabetes. However, this study has been discontinued.

Nanterinone [UK 61260], a phosphodiesterase III inhibitor, was undergoing II evaluation with Pfizer in the US for the treatment of heart failure. Nanterinone is a positive inotropic and balanced-type vasodilating drug, only partially based on phosphodiesterase III inhibition. Preliminary data from controlled studies suggest satisfactory long-term efficacy and safety.

Evatanepag (CP-533,536) is a prostaglandin E2 EP2 receptor agonist. It stimulates new bone formation on trabecular, endocortical, and periosteal surfaces and enhances fracture healing. Evatanepag was under development with Pfizer as a bone formation stimulant for therapeutic use in the healing of fractures.

Traxoprodil (CP-101,606) is a potent, selective N-Methyl-D-aspartate (NMDA) receptor (NR2B subunit) antagonist under development by Pfizer for its potential as a neuroprotectant in head injury and neurodegenerative disease. It is in phase II trials in the US and in phase I in Japan for the potential treatment of head injury, such as, Depressive Disorder, Major and Parkinson's Disease. CP-101,606 does not protect against glutamate-induced neurotoxicity in cultured cerebellar neurons, up to a dose of 10 uM. These results are consistent with CP-101,606 being a potent NMDA antagonist, selective for the type of NMDA receptor associated with the hippocampus. Some further investigation revealed that CP-101,606 was associated with a dose-related dissociation and amnesia. These results support the hypothesis that glutamate antagonists may be useful antidyskinetic agents. However, future studies will have to determine if the benefits of dyskinesia suppression can be achieved without adverse cognitive effects.

Elzasonan (CP 448187) is a serotonin 1B/1D receptor antagonist. Elzasonan was primarily metabolized via oxidative N‐demethylation, N‐oxidation, and aryl hydroxylation. Pfizer was developing elzasonan for the treatment of anxiety and affective disorders however development has been discontinued.

Elzasonan (CP 448187) is a serotonin 1B/1D receptor antagonist. Elzasonan was primarily metabolized via oxidative N‐demethylation, N‐oxidation, and aryl hydroxylation. Pfizer was developing elzasonan for the treatment of anxiety and affective disorders however development has been discontinued.

Crenolanib is an orally active, highly selective, small molecule, next generation inhibitor of platelet-derived growth factor receptor (PDGFR) tyrosine kinase. Crenolanib, manufactured by Arog Pharmaceuticals in Dallas, is taken orally with chemotherapy. The compound is currently being evaluated for safety and efficacy in clinical trials for various types of cancer, including acute myeloid leukemia (AML), gastrointestinal stromal tumor (GIST), and glioma. Crenolanib is an orally bioavailable, selective small molecule inhibitor of type III tyrosine kinases with nanomolar potencies against platelet-derived growth factor receptors (PDGFR) (isoforms PDGFRα and PDGFRβ) and Fms-related tyrosine kinase 3 (FLT3). Besides PDGFR and FLT3, crenolanib does not inhibit any other known receptor tyrosine kinase (RTK) (e.g. VEGFR and FGFR) or any other serine/threonine kinase (e.g., Abl, Raf) at clinically achievable concentrations. Preclinical trials have shown Crenolanib to be active in inhibiting both wild-type and mutant FLT3. Crenolanib is cytotoxic to the FLT3/ITD-expressing leukemia cell lines Molm14 and MV411, with IC50s of 7 nM and 8 nM, respectively. In immunoblots, crenolanib inhibited phosphorylation of both the wild-type FLT3 receptor (in SEMK2 cells) and the FLT3/ITD receptor (in Molm14 cells) in culture medium with IC50s of 1-3 nM. Importantly, the IC50 of crenolanib against the D835Y mutated form of FLT3 was 8.8 nM in culture medium. Furthermore, crenolanib had cytotoxic activity against primary samples that were obtained from patients who had developed D835 mutations while receiving FLT3 TKIs. In vitro, the IC50 of crenolanib for inhibition of FLT3/ITD in plasma was found to be 34 nM, indicating a relatively low degree of plasma protein binding. From pharmacokinetic studies of crenolanib in solid tumor patients, steady state trough plasma levels of roughly 500 nM were found to be safe and tolerable, suggesting that crenolanib could potentially inhibit the target in vivo. Crenolanib has no significant activity against c-KIT, which may be an advantage in that myelosuppression can be avoided.1Furthermore, there was no evidence of QTc prolongation in patients treated with crenolanib. In summary, crenolanib offers a number of advantages over other FLT3 TKIs. Clinical trials of crenolanib in AML patients with FLT3 activating mutations are being planned.

Enazadrem (CP-70490-09) is an antipsoriatic agent inhibiting arachidonate 5-lipoxygenase.

PF-2545920 is an orally-active phosphodiesterase 10A (PDE10A) inhibitor originated by Pfizer, for the treatment of Huntington's disease. PF-2545920 was originally developed by Pfizer for the treatment of schizophrenia. But later clinical studies for Schizophrenia were discontinued. PF-2545920 is a potent and selective PDE10A inhibitor with IC50 of 0.37 nM, with >1000-fold selectivity over the PDE. PF-2545920 is active in a range of antipsychotic models, antagonizing apomorphine-induced climbing in mice, inhibiting conditioned avoidance responding in both rats and mice, and blocking N-methyl-D-aspartate antagonist-induced deficits in prepulse inhibition of acoustic startle response in rats, while improving baseline sensory gating in mice.

PF-2545920 is an orally-active phosphodiesterase 10A (PDE10A) inhibitor originated by Pfizer, for the treatment of Huntington's disease. PF-2545920 was originally developed by Pfizer for the treatment of schizophrenia. But later clinical studies for Schizophrenia were discontinued. PF-2545920 is a potent and selective PDE10A inhibitor with IC50 of 0.37 nM, with >1000-fold selectivity over the PDE. PF-2545920 is active in a range of antipsychotic models, antagonizing apomorphine-induced climbing in mice, inhibiting conditioned avoidance responding in both rats and mice, and blocking N-methyl-D-aspartate antagonist-induced deficits in prepulse inhibition of acoustic startle response in rats, while improving baseline sensory gating in mice.