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Chemical Diversity

The goals of this initiative are two-fold:

  • to support the development of new methodologies related to natural products chemistry; and
  • to support the production of chemical libraries in unexplored regions of “chemical diversity space” where there is reason to believe that novel bioactivities may be found.

Related to the first goal, during the Pilot Phase six R01 grants were made with MLP funds to support the development of new methodologies for natural products chemistry. The rationale behind this funding initiative is that over the years, a large proportion of approved drugs have originated from, or were inspired by, natural products (i.e., small molecules made by specialized pathways, often in plants, marine invertebrates, and microorganisms). This is not surprising, since natural products have evolved in order to enhance the survival of the organisms that produce them–in other words, for their bioactivites. However, in recent years, most pharmaceutical companies have moved away from natural products as leads for drug discovery and development. This often may be due in large part to the limitations of current methodologies for natural products chemistry, including production, isolation, purification, and characterization. This will enhance the availability of biologically active natural products for screening by the MLPCN as well as for drug discovery and development.

The second Chemical Diversity Technology Development goal is being addressed through a series of P41 (Biotechnology Research Resource) grants. Under the terms of these grants, the grantees are providing novel libraries to the MLSMR, for HTS evaluation by the MLPCN. A key provision of this funding initiative is that the library designs are driven by biological rather than purely chemical considerations. Additionally, since the goal is to identify effectors of truly novel biological phenotypes and mechanisms, the compounds produced under this initiative represent chemotypes that are distinct from what is available commercially and in existing compound collections.

The projects funded under RFA-RM-05-013 and RFA-08-004 are designed to address such bottlenecks and to afford improved procedures.

Links to all current MLI funding opportunities: Funding Opportunities

For information about the current Pilot Scale Libraries for High-Throughput Screening (P41) RFA, see RFA-RM-08-003.

For information about the current New Methodologies for Natural Products Chemistry (R01) RFA, see RFA-RM-08-004.

For more information, please contact:

John M. Schwab, Ph.D.
National Institute of General Medical Sciences