A New Natural Products Library Comes to Town

By Eric Sauter

It has taken Ben Shen, a professor on The Scripps Research Institute’s (TSRI) Florida campus, about two years to put together a new library of natural products, but now the results are in and he’s excited.

As of today, TSRI scientists can now access libraries of compounds for screening that include 400 pure natural products, 1,200 partially purified fractions, and 5,500 crude extracts, isolated from 2,100 actinomycetes, which are soil bacteria collected from diverse ecological niches. The Natural Products Library is growing at the rate of about 100 strains/month and all the crude extracts, fractions, and pure natural products that come from those new strains.

As Shen points out, natural products remain the best source of drugs and drug leads, despite the fact that during the past two decades the pharmaceutical industry has been turning more frequently to high throughput screening of synthetic libraries.

Statistics on the general success of natural products run in Shen’s favor. He points out that from the 1940s to the present, 131 out of 175 small molecule anticancer drugs are natural product-based/inspired, with 85 being either natural products or derivatives. From 1981 to date, 79 out of 99 small molecule anticancer drugs are natural product-based/inspired, with 53 being either natural products or derivatives. Among the 20 approved small molecule New Chemical Entities (NCEs) in 2010, a half of them are natural products.

In spite of the great success of natural products in the history of drug discovery, natural products are significantly underrepresented in current small molecule libraries, but now that Shen is building his new library, the future of microbial natural product drug discovery and development at TSRI has become a whole lot brighter.

“The design of our library is unique,” he said. “The real beauty is that our compounds are from strains that are not available in public collections. Each member of the library can be produced in sufficient quantities by microbial fermentation to support follow-up studies. Realization of the full potential of the library really depends on how many people use it. If they get excited and make widespread use of it, then we can grow it dynamically.”

His goal is to eventually produce a library of pure natural products, partially purified fractions, and crude extracts from 10,000 strains, which would provide unprecedented molecular diversity and an outstanding opportunity to screen for drug discovery.

Additional information of the Natural Products Library can be accessed through the NPLI at TRSI website (http://www.scripps.edu/shen/NPLI/npliattsri.html). Shen welcomes collaborative opportunities and can be reached at shenb@scripps.edu.

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