Natural products are the best validated starting points for drug discovery. Our drug discovery and development platform is natural products-centric and covers the entire range from the identification of unexplored organisms, particularly microbes with high biosynthetic capacity, as the starting point for our Genomes to Natural Products to Drugs initiative. CNPD3 members generate and annotate diverse natural and synthetic chemical libraries for phenotypic and target-based screening and subsequent medicinal chemistry efforts and use synthetic biology approaches to manipulate microbial natural products chemistry. Additionally, we are evaluating the scientific basis for pharmacological effects of selected dietary components and ethnobotanicals to characterize the active ingredients (more information about ethnobotanicals and functional foods is available here). Research programs include characterization and the mechanisms of action of drug candidates at the cellular and molecular level and artificial intelligence (AI)-enabled and structure-based drug design to identify or improve on candidate compounds with identified targets. In parallel, we utilize targeted protein degradation (TPD) by proteolysis-targeting chimera (PROTAC) as a platform to develop innovative drug candidates and tool molecules for biological studies. Towards translation of the most promising discoveries, we are using state-of-the-art in vivo models that are most predictive for activity in a clinical setting. Our disease focus is on cancer as well as inflammation, drug abuse, addiction and pain as the major indications, and we collaborate with other centers on our leads in infectious diseases and other important disease areas.
The entire spectrum of multidisciplinary research from genomes to drugs, including mining of unexplored marine microbial genomes, biosynthetic engineering, chemical synthesis and biological profiling of natural products and natural product-like compounds, leading to the corresponding in vitro and in vivo pharmacology, mechanistic studies and preclinical evaluation of drug candidates is depicted above. The D3 platform is supported by the NIH Collaborative Program Grant for Multidisciplinary Teams (RM1) Integrative Multidisciplinary Discovery Platform to Unlock Marine Natural Products Therapeutic Opportunities and other federal and state grants. We have several collaborative cores in the main areas of the D3 process and integrate AI at various levels, including genome mining, machine-learning-based drug screening and optimization. We can also take advantage of the Genome Portal of the Natural Products Discovery Center, or NPDC, at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, for complementary terrestrial microbial genomes as starting points for our natural product discovery. For bioanalytical testing, including pharmacokinetic studies, prioritized candidate compounds may be evaluated in the DMPK Core at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, exclusively working on non-GMP and preclinical analysis, and the UF CTSI Translational Drug Development (TDD) Core, which is performing preclinical stage analysis but also supports clinical trials, complementing DMPK @ UF Scripps.
Focus Areas
Collaborate with CNPD3 Cores (Contacts)
- Microbial Genomics and Synthetic Biology: Yousong Ding, Ph.D. (YDing@cop.ufl.edu)
- Molecular Diversity and Screening: Ranjala Ratnayake, Ph.D. (rratnayake@ufl.edu)
- AI-Based and Structure-Based Drug Design & Optimization: Gustavo Seabra, Ph.D. (seabra@cop.ufl.edu)
- Synthetic Chemistry: Qi-Yin Chen, Ph.D. (chenqyufl@ufl.edu)
- Targeted Protein Degradation: Guangrong Zheng, Ph.D. (zhengg@cop.ufl.edu)
- Botanical Translational Science: Chengguo (CX) Xing, Ph.D. (chengguoxing@cop.ufl.edu)
- Behavioral Pharmacology: Jenny Wilkerson, Ph.D. (jenny.wilkerson@cop.ufl.edu)
Please submit a two-page proposal to the respective core leaders if you would like to collaborate with us. The proposals will be evaluated by a committee on a monthly basis. General questions can be directed to Hendrik Luesch at luesch@cop.ufl.edu. Your proposal should briefly cover the following:
- Significance & unmet clinical need
- Screening/assay details
- Secondary assays and animal models available
- Translational plans and capabilities
- Timeline
- Availability of pilot funds/grants