Events

Development of Pan-Viral Nucleoside Inhibitors

Events in November 2024

Development of Pan-Viral Nucleoside Inhibitors

Non-canonical Paneth cell functions regulate intestinal inflammatory response

New Approaches to Tuberculosis Therapeutics

2024 WARF Therapeutics Distinguished Lecture in Drug Discovery

Join us for a 1-hour session to explore UW’s nationally recognized clinical training approach and how it complements classroom learning, preparing you to become a successful pharmacist.

Pharmaceutical Sciences Seminar Series

Pharmaceutical Sciences Seminar Series

Pharmaceutical Sciences Seminar Series

3:30 PM – 4:30 PM
November 1, 2024

(Drug DISCOVERY Specific Seminar)

Kathie Seley-Radtke, PhD
University of Maryland

The severity and rapid spread of the coronavirus pandemic served to drive home that we were completely unprepared to fight such an outbreak. As a result, it became clear that there was a critical need for small molecule, orally bioavailable, broad-spectrum drugs that could be stockpiled and readily distributed when the next outbreak occurs. In that regard, for many years nucleos(t)ides have maintained a prominent role as one of the cornerstones of antiviral and anticancer therapeutics, and numerous scaffolds in nucleos(t)ide and nucleic acid drug design have been pursued. One such approach involves adding flexibility to the sugar moieties of nucleos(t)ides, for example, in the highly successful anti-HIV/HBV drug Tenofovir developed by Antonín Holý. In contrast, introduction of flexibility to the nucleobase scaffold has only more recently gained significance with the invention of our fleximers. This modification has led to a significant improvements in antiviral activity, and in some cases endowing the nucleoside with potent broad-spectrum activity across several viral families, when the parent rigid nucleoside was inactive. Another advantage observed is the ability to avoid resistance mechanisms related to point mutations by engaging secondary amino acid residues not previously involved in the mechanism of action. A second series of nucleosides being pursued in our group, involves insertion of a heterocyclic spacer ring in between the two moieties of the bicyclic purine ring system, forming an expanded tricyclic nucleoside with increased aromaticity. This modification has also led to potent antiviral activity, again targeting several different pathogens of pandemic concern. A brief history of their design, synthesis, and recent antiviral findings for these innovative nucleos(t)ide scaffolds will be discussed.

Hosted by Jennifer Golden

2006 Rennebohm Hall

777 Highland Ave

Madison, WI 53705

United States

Map

1 3:30 PMDrug DISCOVERY Specific Seminar – Kathie Seley-Radtke, PhD 3:30 PM – 4:30 PM November 1, 2024 Pharmaceutical Sciences Seminar Series (Drug DISCOVERY Specific Seminar) Kathie Seley-Radtke, PhD University of Maryland Development of Pan-Viral Nucleoside Inhibitors The severity and rapid spread of the coronavirus pandemic served to drive home that we were completely unprepared to fight such an outbreak. As a result, it became clear that there was a critical need for small molecule, orally bioavailable, broad-spectrum drugs that could be stockpiled and readily distributed when the next outbreak occurs. In that regard, for many years nucleos(t)ides have maintained a prominent role as one of the cornerstones of antiviral and anticancer therapeutics, and numerous scaffolds in nucleos(t)ide and nucleic acid drug design have been pursued. One such approach involves adding flexibility to the sugar moieties of nucleos(t)ides, for example, in the highly successful anti-HIV/HBV drug Tenofovir developed by Antonín Holý. In contrast, introduction of flexibility to the nucleobase scaffold has only more recently gained significance with the invention of our fleximers. This modification has led to a significant improvements in antiviral activity, and in some cases endowing the nucleoside with potent broad-spectrum activity across several viral families, when the parent rigid nucleoside was inactive. Another advantage observed is the ability to avoid resistance mechanisms related to point mutations by engaging secondary amino acid residues not previously involved in the mechanism of action. A second series of nucleosides being pursued in our group, involves insertion of a heterocyclic spacer ring in between the two moieties of the bicyclic purine ring system, forming an expanded tricyclic nucleoside with increased aromaticity. This modification has also led to potent antiviral activity, again targeting several different pathogens of pandemic concern. A brief history of their design, synthesis, and recent antiviral findings for these innovative nucleos(t)ide scaffolds will be discussed. Hosted by Jennifer Golden 2006 Rennebohm Hall 777 Highland Ave Madison, WI 53705 United States Map Read more

8 1:00 PMDrug ACTION Specific Seminar – Nan Gao, PhD 1:00 PM – 2:00 PM November 8, 2024 Pharmaceutical Sciences Seminar Series (Drug ACTION Specific Seminar) Nan Gao, PhD Rutgers University Non-canonical Paneth cell functions regulate intestinal inflammatory response Paneth cells are the primary source of C-type lysozyme, a β-1,4-N-acetylmuramoylhydrolase that enzymatically processes bacterial cell walls. Aberrant lysozyme production are hallmarks of inflammatory bowel disease (IBD) pathology. I will show experiments that demonstrate the impact of lack or ectopic lysozyme production on colonic inflammation. I will also show data about how Lyz1-deficiency modulates the gut bacterial composition and intestinal immune responses to bacterial molecular patterns. I will present biochemical and immunology evidence to suggest that Paneth cell lysozyme balances intestinal anti- and pro-inflammatory responses. In addition, I will shed light on our recent finding that a direct engagement of intestinal lysozyme with enteric pathogens such as Salmonella promotes the release of bacterial virulence factors that are barrier-impairing and pro-inflammatory. In the end I’ll discuss our ongoing work investigating the Paneth cell subsets that may be important for host responses to infection and inflammation. Hosted by Ting Fu 1116 Rennebohm Hall 777 Highland Ave Madison, WI 53705 United States Map Read more

12 6:00 PMThe UW Difference: PharmD Clinical Training 6:00 PM – 7:00 PM November 12, 2024 Join us for a 1-hour session to explore UW’s nationally recognized clinical training approach and how it complements classroom learning, preparing you to become a successful pharmacist. Learn about the core of our clinical training program — Introductory and Advanced Pharmacy Practice Experiences.Discover how these real-world rotations shape your PharmD education and prepare you for your career. Dive into our 1,500+ full-time clinical rotations offered across Wisconsin, the nation, and international locations, and see real examples of these diverse experiences. Hear a current student’s take on UW clinical training life, get insights from expert faculty, and see how our approach leads to top residencies and successful careers. Get your questions answered by those who’ve walked and taught the UW–Madison clinical training program. Offered virtually on Zoom on Tuesday, November 12 at 6:00 p.m. – 7:00 p.m. CST Register now! Zoom Read more

15 3:30 PMWARF Therapeutics Distinguished Lecture in Drug Discovery: Jeffrey Aube, PhD 3:30 PM – 4:30 PM November 15, 2024 2024 WARF Therapeutics Distinguished Lecture in Drug Discovery Jeffrey Aube, PhD University of North Carolina New Approaches to Tuberculosis Therapeutics Tuberculosis (TB) continues to be a major worldwide health problem, despite the existence of numerous drugs for its treatment. This is in part due to the long therapeutics times required to administer cocktails of front-line therapeutics and in part due to the emergence of even more challenging long-term strains. For these reasons, new therapeutic agents for the treatment of TB continue to be sought. In collaborative work with the laboratory of Carl Nathan (Weill–Cornell Medicine) and others, we have sought to find new chemotypes as potential anti-TB agents and to identify new biochemical targets for drug treatment. In this talk, I will describe our efforts in this area, beginning with early approaches to explore beta-lactam antibiotics as possible TB agents. More recent efforts have been focused on finding inhibitors of phosphopantetheinyl transferase (PptT). PptT carries out central biochemistry that is essential for mycobacterial survival; for this reason, it has been a long sought-target for antibacterial agent development. This story begins with our team’s discovery of the first effective small-molecule inhibitors of PptT, efforts to use bioisostere design to create a new series, and more recent chemotypes of PptT. Hosted by Jennifer Golden 2006 Rennebohm Hall 777 Highland Ave Madison, WI 53705 United States Map Read more

23 8:30 AMUW–Madison PharmD Preview Day 8:30 AM – 12:30 PM November 23, 2024 Join us for these Preview Day sessions: PharmD Admissions Overview Financial Aid and Scholarship Opportunities Experience a Cool Lab Simulation Led by Current Students Connect With Our Students for an Insightful Q&A Session Hear from Pharmacists About Their Unique Field of Pharmacy Tour our Cutting-Edge Research Facilities Register Today! Commons – Rennebohm Hall 777 Highland Ave Madison, WI 53705 United States Map Read more