MOLECULAR LIBRARIES HIGH THROUGHPUT SCREENING CENTERS:  REQUEST FOR 
INFORMATION (RFI)

RELEASE DATE:  November 21, 2003

NOTICE:  NOT-RM-04-001 (formerly NOT-MH-03-010)

National Institutes of Health (NIH) 
 (http://www.nih.gov)

This RFI is for a roadmap initiative.  All NIH Institutes and Centers 
participate in roadmap initiatives.

The National Institutes of Health (NIH) is planning to establish a network of 
Molecular Libraries Screening Centers as a national resource for biomedical 
research.  The proposed network would provide capability for high throughput 
screening (HTS) of a public collection of chemically diverse small molecules 
(which will be assembled by NIH in a complementary effort) by a variety of 
assays to identify the potential of the molecules in the collection for use 
as biological probes and as starting points for the development of 
therapeutics.  The chemical structures of compounds in the small molecule 
repository and the screening data generated by the centers will be made 
available in a public cheminformatics database (also being developed 
separately).  NIH plans to issue a Request for Applications to establish a 
network of pilot screening centers in mid-January 2004, with a receipt date 
in mid-June 2004, and an anticipated award date in May 2005.

NIH is aware of the growing interest and involvement of the academic 
community in the development of compound libraries, as well as screening, 
chemical genomics, and drug discovery capacities.  Through this Request for 
Information (RFI), NIH would like to obtain information that is relevant to 
establishing a pilot HTS center program, and to identify interested sources 
that are already developing existing screening capabilities or that could 
develop the infrastructure support and capabilities for HTS screening, to 
facilitate the Molecular Libraries Roadmap program 
(http://nihroadmap.nih.gov/molecularlibraries/index.asp) and aid in the 
planning of this new initiative.  

This RFI is for information and planning purposes only and should not be 
construed as a solicitation or as an obligation on the part of the 
Government.  The Government does not intend to award a cooperative agreement 
on the basis of responses to this RFI nor otherwise pay for the preparation 
of any information submitted or for the Government’s use of such information.  

Background 

The NIH wishes to facilitate the use of HTS to identify small molecules that 
have the potential for use as chemical probes to study cellular pathways and 
the functions of major components of the cell in health and disease by 
rapidly and efficiently screening a large number of compounds that 
encompasses a broad range of novel targets and activities.  The intent of the 
program is to benefit basic biological research and preclinical research by 
increasing the variety of available bioactive compounds, and to increase the 
number of molecules available as potential drug candidates for further 
development by the public or private sector.  Data from HTS assays will be 
made available to investigators through a publicly accessible cheminformatics 
database.  

The Molecular Libraries Screening Center program is designed to empower 
multi-disciplinary academic teams to discover small molecules that can be 
used in basic biological and biomedical studies, and to translate basic 
research findings into novel therapeutics in disease areas that may not be 
attractive to the private sector. The sharing of small molecules, assays, and 
screening data with the larger scientific community represents a new public 
sector paradigm that promises to facilitate the understanding of basic 
biological mechanisms and shorten the timeline for drug development, with 
resulting benefits to public health, especially for rare disorders.

The NIH is planning to use a cooperative agreement mechanism to establish 8-
10 pilot screening centers in FY 2005 with the capabilities to:  1) adapt 
target-based and cell-based phenotypic assays solicited from investigators in 
the public or private sector to HTS format; 2) screen small molecule 
libraries for biological activity in these assays; c) provide 
medicinal/optimization chemistry to transform screening hits into useful 
biological probes; and d) support informatics capability to track compounds 
and assays.  During the initial 3-year phase, the pilot centers will be 
expected to increase their capabilities and throughput to achieve a minimum 
goal of screening 100,000 small molecules in each of 20 assays per year.  The 
pilot program will lay the groundwork for a subsequent solicitation for a 
smaller number of fully operational, larger scale HTS centers.   

Information Requested

Information in the following areas will aid the NIH in the design of the 
announcement for pilot HTS centers.  We ask that interested organizations 
identify critical criteria that should be included in the announcement and to 
describe their interests as well as their current and potential capabilities 
to meet these criteria.  Information presented need not be limited to these 
areas.  Please limit your responses to 10 pages or less.

1. Modification of Assays for HTS

a.  Describe your capabilities, or means of acquiring the capabilities, to 
modify experimental in vitro assays to produce assay protocols suitable for 
HTS.  Assays that you have developed may be listed, as well as the technical 
capabilities of personnel and the capacity available in your organization.

b. Describe the criteria by which you would judge the usefulness of an assay 
for identification of research tools or candidates for drug development, and 
how you think that a center should prioritize and coordinate the screening of 
multiple assays.

c. Describe your LIMS (laboratory information management system) and your 
capabilities for data analysis, including structure-activity analysis.

2.  Equipment/Techniques

a.  Describe your current facilities and equipment, or plans to acquire the 
appropriate infrastructure support, and discuss the range of techniques and 
technologies available in your organization.

3.  Capacity

a.  Describe the level of throughput obtainable with your current level of 
staff and equipment including number of viable assays and estimated number of 
molecules that could be screened per year.

b.  Describe the highest level of throughput likely to be obtainable by your 
organization and discuss the timeline, staff, and equipment additions you 
believe would be necessary to reach this level. 

4. Personnel

a.  Describe the personnel who would be required to modify, screen, and 
analyze one assay.  Include an estimate for the level of effort of each.

Responses

Responses should be identified with RFI No., and are due by December 17, 
2003.  Please submit three (3) copies of your response, to Linda Brady, PhD, 
NIH contact for the Molecular Libraries Screening Centers Initiative, 
National Institute of Mental Health, NIH, 6001 Executive Boulevard, Room 
7185, Bethesda, MD 20892-9641 (For FedEx or courier, use: Rockville, MD 
20852). Email responses will also be accepted at lbrady@mail.nih.gov

For further information on this or other NIH Roadmap Molecular Libraries 
initiatives, please contact the NIH implementation group members listed at 
http://nihroadmap.nih.gov/molecularlibraries/members.asp

Acknowledgment of receipt of responses will not be made, nor will respondents 
be notified of the Government’s assessment of the information received. 
However, should such an announcement materialize, no basis for claims against 
the Government shall arise as a result of a response to this request for 
information or the Government’s use of such information as either part of our 
evaluation process or in developing specifications for any subsequent 
announcement.  Responses will be held in a confidential manner.  Any 
proprietary information should be so marked.

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