Natural Product Libraries and High-Throughput Screening Core (NPS Core)

Natural Product Libraries and High-Throughput Screening Core (NPS Core)

The difficulty and opportunity of drug discovery from natural products

Natural products have always been an important source of drug development. However, with the development of HTS technology, synthetic small molecule compound libraries which are built based on combinatorial chemistry are the main focus of drug discovery. Combinatorial chemistry can quickly provide a large number of small molecule compounds. However, the results of many large screens have been disappointing in practice. It was recognized that combinatorial chemistry techniques may not able to fulfill the expectation that could provide all the chemicals needed for successful lead discovery. Researchers have also realized that “chemical diversity” is more important than the size of libraries (number of compounds). Analysis of the new approved therapeutic agents by US FDA from 2001 to 2019 revealed that 24.6% are synthetic drugs; by contrast,49% are natural products, natural derivatives, synthetic compounds derived from natural product pharmacophores, or botanic drugs (mixture of natural compounds). One of the decisive factors is that natural product collections exhibit a wide range of pharmacophores and a high degree of stereochemistry. This indicated that natural products are still an irreplaceable resource for drug discovery. However, it is a time- and labor-consuming work to isolate pure compounds from natural materials; and usually only limited variety and quantities of pure compounds are obtained. In addition, the high stereo-chemical diversity properties of natural products also hugely increase the difficulties in synthesis of natural products. Thus, pure compound library of natural product is not commonly available. These factors make it difficult to apply HTS approaches for drug discovery from natural product. In order to strike a balance between chemical diversity, drug library size, and various costs of drug library preparation, researchers have begun to use pre-fractioned library for HTS. A crude extract is divided into tens to hundreds of fractions. Small quantities of crude extracts are enough for the preparation of library with large number of fractions for biological tests. Furthermore, the bottleneck of the isolation and structure-elucidation of active component in fractions can also be addressed by sensitive NMR techniques.

About NPS Core lab

1. Goal: Providing diversified and stable natural product libraries and high-throughput screening services; and becoming a high-quality platform to help natural product drug discovery research of academic and industrial fields.
2. Our service: This platform integrates the existing natural product resources and high-throughput screening equipment in KMU. Our service starts with a consultation with users on the ultimate goal, target and assay methods of screening, establishment and optimization of screening assay, high-throughput screening, hits verification, chemical characterization of active fractions, and identification of indicators/active ingredients. We will bridge user and our supporting laboratories to build a drug discovery research team. According to users demand, customized services is can be integrated with our standardized models.
3. Our capacity: We offer three natural product libraries. The first one is the Taiwan indigenous plant extract library, which contains extracted 3,000 extracts. The second library is Dr. Cecilia Koo Botanic Conservation Center (KBCC)-library, which contains 2,889 extracts. The third library is pre-fractioned library, which contains 6,240 fractions. We equipped with an automatic liquid handling workstation, an automatic multimode plate reader, and a high-content system. Our screening capacity is around 2,000~4,000 tests/day. Absorbance, fluorescence, luminance, or image based assays are all applicable on our platform.

Main researcher Intro.

PI of NPS Core: Chia-Hung Yen, (Associate Professor, Graduate Institute of Natural Products) who responsible for the management, construction and maintenance of natural product libraries and high-throughput/high content screening services.

Natural product chemistry teams: KMU has long and rich experience on natural product research. Thus, we have strong supported labs led by Prof. Hsun-Shuo Chang at School of Pharmacy, and Prof. Fang-Rong Chang and Prof. Yuan-Bin Cheng at Graduate Institute of Natural Products. (Prof. Yuan-Bin Cheng currently teaches at Department of Marine Biotechnology and Resources, National Sun Yat-Sen University. Extracts preparation for libraries construction was carried out by Prof Cheng's lab in KMU)

Plant material supporting team: Dr. Cecilia Koo Botanic Conservation Center of which Prof. Chia-Wei Li at Institute of Molecular and Cellular Biology, National Tsing Hua University is the CEO.

Website of NPS Core: https://nps.kmu.edu.tw/

E-mail address of CH Yen: chyen@kmu.edu.tw