PF-03654764 binds with high affinity to the human H3 receptor and with lower affinity to the rat H3 receptor, in addition to having >1000-fold selectivity versus other human histamine receptor subtypes (H1, H2, and H4). PF-03654764 displayed potent antagonist properties in functional assays measuring cAMP utilizing a reporter gene assay (β-lactamase) in HEK293 cells stably expressing full length human or rat H3 receptors. In human hepatic microsomes, PF-03654764 was metabolically stable and were predicted to have low clearance. It has low potential to inhibit activities of CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4. PF-03654764 + fexofenadine failed to provide superior relief of allergic rhinitis-associated nasal symptoms upon exposure to ragweed pollen compared to fexofenadine + pseudoephedrine. Side effects in the PF-03654764-treated groups were clinically significant compared to the controls. PF-03654764 had been in phase II clinical trial for the treatment of allergic rhinitis and in phase I clinical trial for the treatment of Alzheimer's disease. However, these investigations were discontinued.

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.

PF-232798 is a potent oral CCR5 antagonist with a primary and selectivity/safety pharmacology profile similar to maraviroc (MVC). PF-232798 shows increased binding affinity and improved oral absorption compared to maraviroc. In addition, it retains activity against a laboratory generated maraviroc-resistant HIV-1 strain, indicating an alternative drug resistance profile. PF-232798 binds to the same pocket as MVC within the transmembrane region of CCR5, but shows additional interactions at the ECL2 hinge region. PF-232798 is well tolerated in normal volunteers. PF-232798 had been in a phase-II clinical trial for the treatment of HIV infections. 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.

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.

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.

Zoniporide hydrochloride is a novel, potent and selective NHE-1 inhibitor (IC50 = 14 nM). Reduces infarct size in the isolated heart (EC50 = 0.25 nM). Attenuates post-ischemic cardiac contractile dysfunction and ischemia-reperfusion-induced ventricular fibrillation in vivo. Zoniporide hydrochloride represents a novel class of potent and selective human NHE-1 inhibitors with potential utility for providing cardioprotection in a clinical setting.

Zoniporide hydrochloride is a novel, potent and selective NHE-1 inhibitor (IC50 = 14 nM). Reduces infarct size in the isolated heart (EC50 = 0.25 nM). Attenuates post-ischemic cardiac contractile dysfunction and ischemia-reperfusion-induced ventricular fibrillation in vivo. Zoniporide hydrochloride represents a novel class of potent and selective human NHE-1 inhibitors with potential utility for providing cardioprotection in a clinical setting.

Teloxantrone (also known as DuP 937) was developed as an anthrapyrazole intercalator that inhibits DNA synthesis. Teloxantrone interacts with topoisomerase II, thereby inhibiting DNA replication and repair, as well as RNA and protein synthesis. The drug participated in phase II clinical trials in colorectal carcinoma, in non-small cell lung cancer, in metastatic malignant melanoma. However, these studied apparently were discontinued.

Zoniporide hydrochloride is a novel, potent and selective NHE-1 inhibitor (IC50 = 14 nM). Reduces infarct size in the isolated heart (EC50 = 0.25 nM). Attenuates post-ischemic cardiac contractile dysfunction and ischemia-reperfusion-induced ventricular fibrillation in vivo. Zoniporide hydrochloride represents a novel class of potent and selective human NHE-1 inhibitors with potential utility for providing cardioprotection in a clinical setting.