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The NPLI at TSRI

The Natural Products Library Initiative (NPLI) at TSRI

Natural products possess enormous structural and chemical diversity that is unsurpassed by any synthetic libraries, remain the best sources of drugs and drug leads, but are significantly underrepresented in current small molecule libraries.  The NPLI at TSRI aims at constructing a natural products library to meet the current HTS needs and developing technologies to overcome current challenges in natural products structural diversity and lead optimization.  The NPL at TSRI biases natural products of bacterial origin so that each member of library can be produced in sufficient quantities by large-scale fermentation for follow up mechanistic and preclinical studies and overproducers can be engineered to solve the supply bottleneck for ultimate production and commercialization.

The NPL consists of: (i) purified natural products with fully assigned structures, (b) MPLC (on C-18 semipreparative column) fractions, and (c) crude extracts.  The NPL is presented in 384-well format with all materials dissolved in DMSO (1 mM for pure compounds and 50 mg/mL for fractions and extracts), compatible with most of the HTS platforms.  The NPL currently available for screening includes: (a) 5,500 strains, (b) 450 pure natural products, (c) 3,400 MPLC fractions, and (d) 8,500 crude extracts.  The NPL grows at the rate of 100 strains/month and crude extracts, MPLC fractions, and pure natural products derived thereof.  The NPL provides an unprecedented molecular diversity to screen emerging targets for drug leads, and selected members of the NPL serves as outstanding small molecule probes to interrogate biology.

Lactimidomycin is now available from EMD Millipore (http://www.emdmillipore.com/life-science-research/lactimidomycin/EMD_BIO-506291/p_uuid?WFSimpleSearch_NameOrID=lactimidomycin&BackButtonText=search+results).