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. Genomes are analyzed for biosynthetic potential to discover new natural products that are not expressed under “standard” conditions and require artificial systems for heterologous expression, thereby increasing the pool of screenable natural products and chemical diversity. In parallel we are using classical isolation procedures to directly extract natural products from the producing organisms and subject them to phenotypic and target-based screening campaigns, along with synthetic but natural product-like compounds that are prepared by CNPD3 investigators. CNPD3 members generate and annotate diverse natural and synthetic chemical libraries for screening and subsequent medicinal chemistry efforts and use synthetic biology approaches to manipulate microbial natural products chemistry. We are also evaluating the scientific basis of selected complementary alternative medicine and certain natural product preparations that are being used as part of the diet, dietary supplements or ethnobotanicals, and we are characterizing the active components. More information about ethnobotanicals and functional foods is available here.
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. (firstname.lastname@example.org)
- AI-Based and Structure-Based Drug Design & Optimization: Gustavo Seabra, Ph.D. (email@example.com)
- Synthetic Chemistry: Qi-Yin Chen, Ph.D. (firstname.lastname@example.org)
- PROTAC & Targeted Therapeutics: Guangrong Zheng, Ph.D. (email@example.com)
- Botanical Translational Science: Chengguo (CX) Xing, Ph.D. (firstname.lastname@example.org)
- Behavioral Pharmacology: Jenny Wilkerson, Ph.D. (email@example.com)
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 firstname.lastname@example.org. Your proposal should briefly cover the following:
- Significance & unmet clinical need
- Screening/assay details
- Secondary assays and animal models available
- Translational plans and capabilities
- Availability of pilot funds/grants
The CNPD3 provides both drug discovery expertise and the infrastructure to screen for novel targets and chemical entities that modulate target activity. Specifically, target discovery and validation can be achieved through genomic scale RNAi screening. Validated targets are screened against our drug-like small molecule libraries, especially UF proprietary natural products and natural product-like libraries. Assays can be miniaturized and made “HTS-ready” to allow future high-throughput screens (HTS) at larger screening facilities. Hits can be optimized and developed into probes and/or drug candidates through medicinal chemistry campaigns and interactive pharmacology. CNPD3 investigators characterize the mechanisms of action at the cellular and molecular level and utilize structure-based drug design to improve on candidate compounds with identified targets. Towards translation of the most promising discoveries, we are utilizing state-of-the-art in vivo models that are most predictive for activity in the clinical setting. Our disease focus is on cancer as well as drug abuse/addiction and pain as the major indications and we collaborate with other centers on our leads in infectious diseases and other areas.
The entire spectrum of multidisciplinary research from genomes to drugs, including genome mining, 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. We have several collaborative cores and emerging cores in the main areas of the D3 process. Candidate compounds with promising activity can also be evaluated in UF’s Translational Drug Development (TDD) Core at the Clinical and Translational Science Institute (CTSI) for bioanalytical testing including pharmacokinetic studies.