Taprenepag isopropyl (also known as PF-04217329) a prodrug of CP-544326 (active acid metabolite), a potent and selective EP(2) receptor agonist. Taprenepag isopropyl was studied in a clinical trials phase II involving patients with primary open angle glaucoma. According to Pfizer’s pipelines in May 2011, the study was discontinued.

Cytochalasin D, a tropical fungal metabolite, is a disruptor of actin filament function, resulting in multinucleated cell formation, reversible inhibition of cell movement, and the induction of cellular extrusion. It was shown that cytochalasin D inhibits murine CT26 colorectal carcinoma cells growth and angiogenesis.

Annamycin is a highly lipophilic form of the anthracycline doxorubicin with the ability to bypass multidrug resistance mechanisms of cellular drug resistance. Annamycin belongs to the anthracycline class of drugs, and has a pleiotropic mechanism of action where it targets topoisomerase II, causing strand breaks in DNA. Annamycin forms complexes with DNA by intercalation between base pairs, and it inhibits topoisomerase II activity by stabilizing the DNA-topoisomerase II complex, preventing the religation portion of the ligation-religation reaction that topoisomerase II catalyzes. The agent is being evaluated in separate phase 1 and phase 2 trials in the United States and Europe. Studies in animal models showed the agent to be noncardiotoxic. Trials that included patients with leukemia showed the agent was associated with fewer dose-limiting toxicities than typically experienced with doxorubicin. The FDA granted fast track designation to Annamycin for treatment of patients with relapsed or refractory acute myeloid leukemia.

Fiboflapon sodium (GSK2190915) is a high affinity 5-lipoxygenase-activating protein inhibitor being developed for the treatment of asthma. The compound was originally developed by Amira Pharmaceuticals. Fiboflapon sodium (GSK2190915) exhibits excellent preclinical toxicology and pharmacokinetics in rat and dog. GSK2190915 also demonstrated an extended pharmacodynamic effect in a rodent bronchoalveolar lavage (BAL) model. Oral administration of Fiboflapon sodium (GSK2190915) (1 mg/kg) resulted in sustained inhibition of ex vivo ionophore-challenged whole blood LTB4 biosynthesis with >90% inhibition for up to 12 h and an EC50 of approximately 7 nM. When rat lungs were challenged in vivo with calcium-ionophore, Fiboflapon sodium inhibited LTB4 and cysteinyl leukotriene (CysLT) production with ED50s of 0.12 mg/kg and 0.37 mg/kg, respectively. Fiboflapon sodium is in Phase-II for Asthma (Adjunctive treatment) in Poland, Ukraine, Bulgaria, USA, United Kingdom and Canada (PO).

Diethylhomospermine is the polyamine analogue. It suppressed the activity of the major biosynthetic enzymes, ornithine decarboxylase and S-adenosylmethionine decarboxylase in human bladder cancer cell lines. Diethylhomospermine given as the subcutaneous injection is overall well tolerated at lower doses, but significant toxicities were observed at the 37.5mg/m2/day dose level. Maximal tolerated dose was established at 25 mg/m2/day but further investigation with this study drug is not recommended secondary to the potential for neurotoxicities and hepatic damage as a result of cumulative doses. Diethylhomospermine had been in phase II clinical trials for the treatment of AIDS-related chronic diarrhea. However, this research has been discontinued.

AFN-1252 (now known as Debio-1452) is an antibiotic drug which is in phase II of clinical trials for the treatment of Staphylococcal skin and skin structure infections. The drug was effective in vitro against all isolates of S.aureus and its effect was explained by inhibition of enoyl-acyl carrier protein Reductase (FabI).

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.