The Wertheim UF Scripps Institute Chemical Biology & 5th UF Drug Discovery Symposium

It is our great pleasure to welcome you all to the UF Scripps Chemical Biology & 5^th UF Drug Discovery Symposium (UFDDS). The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology in Jupiter and the Center for Natural Products, Drug Discovery and Development (CNPD3) in Gainesville are joining forces this year to host the event.

The UF Drug Discovery Symposium was established in 2016 and the past four events, held in Gainesville, brought together roughly 200 participants from all Florida research institutions. This year the symposium is designed to celebrate the integration of the Jupiter campus as a new research arm of UF Health by showcasing the combined UF drug discovery expertise at the UF Scripps and the main campus. 

The UF-centric 2023 symposium will feature speakers from both UF campuses and keynote speakers who are global leaders in chemical biology and drug discovery from academia and pharma.

The symposium will cover a range of topics on the use of both natural and synthetic small molecules to monitor and manipulate the proteome. The sessions will cover topics on Control of Protein Homeostasis and Degrader Development, Natural Products, Chemical Proteomics, Drug Development, and Integral Membrane Proteins. We warmly welcome our four keynote speakers: Nathanael Gray (Stanford), Dan Nomura (University of California at Berkeley), Ingrid Wertz (Lyterian), and William Fenical (Scripps Institution of Oceanography, University of California at San Diego) who are outstanding leaders in these fields. In addition, many of our own faculty from the UF Scripps and Gainesville campuses will demonstrate that together we are an even greater powerhouse in drug discovery. The program will include a poster session and an award ceremony recognizing the best poster presenters among our graduate students and postdoctoral researchers.

We hope you all enjoy the joint event this year and use the opportunity to connect with friends and colleagues from both campuses and across Florida.  Go Gators!

Thomas Kodadek, Ph.D. & Hendrik Luesch, Ph.D.

William Fenical 

Scripps Institution of Oceanography
University of California
San Diego, CA 

Marine Polyketide Cancer Drug Candidates: Full Stereochemical Assignments by Genomic Bioinformatics 

Over the past few years, our interest in exploring marine type 1 polyketides and their applications in cancer drug discovery have involved studies of numerous strains of marine-derived bacteria.  These bacteria are actinomycetes assigned to the genera Micromonospora, and Streptomyces, as well as a rare, undescribed new genus.  The polyketides from these strains generally possess more than 16 chiral centers making their assignments one of the most difficult activities in natural products structure elucidation.  With accurate genomic data now available, the stereospecificities of type 1 modular enzymes allows stereochemical assignments with relatively high levels of accuracy.  This presentation illustrates these principles used to assign the full structures of three new classes of polyketides. 

Nathanael S. Gray

Department of Chemical and Systems Biology
Stanford University
Stanford, CA

Proximity Therapeutics as a New Drug Discovery Strategy

Proximity Therapeutics refers to the development of potential therapeutic agents that work by inducing the physical proximity of two biomolecules.  The most well-established classes of proximity therapeutics are bivalent antibodies and small molecule E3 molecular glues that induce protein degradation. A central challenge in proximity-based therapeutics is developing the appropriate chemical matter for inducing the desired protein-protein interactions.  In this talk I will discuss addressing this challenge for protein degraders and transcription-factor chemical induce degrader (TCIPs).  Targeted protein degradation (TPD) refers to the use of small molecules to induce ubiquitin-dependent degradation of proteins. TPD is of interest in drug development, as it can address previously inaccessible targets. However, degrader discovery and optimization remains an empirical process due to a lack of understanding of the relative importance of the key molecular events required to induce target degradation. Here I describe our labs efforts to develop efficient methods to discover and characterize new degraders focused on protein kinase targets.  I will also discuss our labs efforts to develop chemical inducers of proximity to re-wire cellular transcription.  We developed bivalent compounds that recruit the transcriptional co-activator Brd4 to the transcriptional repressor Bcl6 which result in activation of a pro-apoptotic gene expression program. 

Ingrid Wertz

CEO, Lyterian Therapeutics

Co-opting the Ubiquitin System for Therapeutic Benefit

The ubiquitin system is a primary conduit for the regulated degradation of cellular proteins. Ubiquitination describes the covalent modification of protein substrates with ubiquitin, a small protein that binds the proteasome and directs substrate degradation. Our goal is to co-opt the ubiquitin system, and more broadly protein homeostasis, to irreversibly regulate challenging therapeutic targets for enhanced clinical efficacy. Our efforts are focused on targets for which there is a clear rationale for homeostatic regulation over target inhibition. We will discuss strategies to co-opt protein homeostasis, highlight mechanisms for how selective targeting can be achieved, and review the cellular and physiological consequences of target regulation, with an emphasis on maximizing safety and therapeutic benefit for patients.

Dan Nomura

Berkeley College of Chemistry
University of California – Berkeley
Berkeley, CA

Reimagining Druggability using Chemoproteomic Platforms

The Nomura Research Group is focused on reimagining druggability using chemoproteomic platforms to develop transformative medicines. One of the greatest challenges that we face in discovering new disease therapies is that most proteins are considered “undruggable,” in that most proteins do not possess known binding pockets or “ligandable hotspots” that small-molecules can bind to modulate protein function. Our research group addresses this challenge by advancing and applying chemoproteomic platforms to discover and pharmacologically target unique and novel ligandable hotspots for disease therapy.