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Articles 1 - 5 of 5
Full-Text Articles in Medicine and Health Sciences
Target Repurposing For Neglected Diseases, Michael P. Pollastri, Robert K. Campbell
Target Repurposing For Neglected Diseases, Michael P. Pollastri, Robert K. Campbell
Michael Pollastri
Infectious diseases are an enormous burden to global health, and since drug discovery is costly, those infectious diseases that affect the developing world are often not pursued by commercial drug discovery efforts. Therefore, pragmatic means by which new therapeutics can be discovered are needed. One such approach is target repurposing, where pathogen targets are matched with homologous human targets that have been pursued for drug discovery for other indications. In many cases, the medicinal chemistry, structural biology, and biochemistry knowledge around these human targets can be directly repurposed to launch and accelerate new drug discovery efforts against the pathogen targets. …
Synthesis And Evaluation Of Human Phosphodiesterases (Pde) 5 Inhibitor Analogs As Trypanosomal Pde Inhibitors. 1. Sildenafil Analogs, Cuihua Wang, Trent D. Ashton, Alden Gustafson, Nicholas D. Bland, Stefan O. Ochiana, Robert K. Campbell, Michael P. Pollastri
Synthesis And Evaluation Of Human Phosphodiesterases (Pde) 5 Inhibitor Analogs As Trypanosomal Pde Inhibitors. 1. Sildenafil Analogs, Cuihua Wang, Trent D. Ashton, Alden Gustafson, Nicholas D. Bland, Stefan O. Ochiana, Robert K. Campbell, Michael P. Pollastri
Michael Pollastri
Parasitic diseases, such as African sleeping sickness, have a significant impact on the health and well-being in the poorest regions of the world. Pragmatic drug discovery efforts are needed to find new therapeutic agents. In this report we describe target repurposing efforts focused on trypanosomal phosphodiesterases. We outline the synthesis and biological evaluation of analogs of sildenafil (1), a human PDE5 inhibitor, for activities against trypanosomal PDEB1 (TbrPDEB1). We find that, while low potency analogs can be prepared, this chemical class is a sub-optimal starting point for further development of TbrPDE inhibitors.
Synthesis And Evaluation Of Human Phosphodiesterases (Pde) 5 Inhibitor Analogs As Trypanosomal Pde Inhibitors. 2. Tadalafil Analogs, Stefan O. Ochiana, Alden Gustafson, Nicholas D. Bland, Cuihua Wang, Michael J. Russo, Robert K. Campbell, Michael P. Pollastri
Synthesis And Evaluation Of Human Phosphodiesterases (Pde) 5 Inhibitor Analogs As Trypanosomal Pde Inhibitors. 2. Tadalafil Analogs, Stefan O. Ochiana, Alden Gustafson, Nicholas D. Bland, Cuihua Wang, Michael J. Russo, Robert K. Campbell, Michael P. Pollastri
Michael Pollastri
In this report we describe our ongoing target repurposing efforts focused on discovery of inhibitors of the essential trypanosomal phosphodiesterase TbrPDEB1. This enzyme has been implicated in virulence of Trypanosoma brucei, the causative agent of human African trypanosomiasis (HAT). We outline the synthesis and biological evaluation of analogs of tadalafil, a human PDE5 inhibitor currently utilized for treatment of erectile dysfunction, and report that these analogs are weak inhibitors of TbrPDEB1.
Identification And Characterization Of Kava-Derived Compounds Mediating Tnf-Α Suppression, Michael P. Pollastri, Adrian Whitty, Jamie Cassidy Merrill, Trent D. Ashton, Salomon Amar
Identification And Characterization Of Kava-Derived Compounds Mediating Tnf-Α Suppression, Michael P. Pollastri, Adrian Whitty, Jamie Cassidy Merrill, Trent D. Ashton, Salomon Amar
Michael Pollastri
There is a substantial unmet need for new classes of drugs that block TNF-α-mediated inflammation, and particularly for small molecule agents that can be taken orally. We have screened a library of natural products against an assay measuring TNF-α secretion in lipopolysaccharide (LPS)-stimulated THP-1 cells, seeking compounds capable of interfering with the TNF-α inducing transcription factor Lipopolysaccharide Induced TNF Alpha Factor (LITAF). Among the active compounds were several produced by the kava plant (Piper mysticum), extracts of which have previously been linked to a range of therapeutic effects. When tested in vivo, a representative of these compounds, kavain, was found …
The Challenge Of Developing Robust Drugs To Overcome Resistance, Celia Schiffer, Amy C. Anderson, Michael P. Pollastri, Norton P. Peet
The Challenge Of Developing Robust Drugs To Overcome Resistance, Celia Schiffer, Amy C. Anderson, Michael P. Pollastri, Norton P. Peet
Michael Pollastri
Drug resistance is problematic in microbial disease, viral disease and cancer. Understanding at the outset that resistance will impact the effectiveness of any new drug that is developed for these disease categories is imperative. In this Perspective, we detail approaches that have been taken with selected drug targets to reduce the susceptibility of new drugs to resistance mechanisms. We will also define the concepts of robust drugs and resilient targets, and discuss how the design of robust drugs and the selection of resilient targets may lead to successful strategies for combating resistance.