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Molecular Libraries and Imaging Roadmap Program


Interrelationship between Blueprint and Roadmap

 

Objective

  The Program that this Announcement describes is one component of the NIH Roadmap Molecular Libraries and Imaging Initiative.  It provides $100K of funding in Year 1 (via the R21 mechanism) to develop and characterize assays to novel targets, pathways and cellular phenotypes that can be miniaturized and automated.  The objective of the Program is to develop assays that can be used to identify small molecule interactions via high-throughput screening (HTS) of small molecular compound libraries, and to chemically optimize these active compounds as molecular probes.  For this reason, the Program provides rapid “Fast-Track” access, and $25K of additional funding, for HTS-ready assay projects that enter the Roadmap Molecular Library Screening Center Network (MLSCN) in Year 2 of the award.

Assay Format

All applications should provide a rationale for how the availability of a small molecule molecular probe would add a pharmacological dimension to their work that is not currently possible.  In addition, Investigators should define the attributes to be captured in the design of this probe, and provide a plan for developing and characterizing assays that could be used to identify small molecules with essential probe attributes from a large diversity collection of >300,000 small molecules.  Emphasis will be placed on the screening of targets for which selective and potent small molecule modulators are not currently available.

Particularity of the program

The overall goal of the Roadmap Molecular Library Initiative is to promote the development of small molecule pharmacological tools, and to also facilitate the creation of a PubChem database matching biological assays (for targets, pathways or phenotypes) to small molecules that have activity in these assays.  This is being accomplished through the creation of the MLSCN, a national network of 10 high-throughput Screening Centers. 

  1. The NIH accepts probe development projects for assignment to the MLSCN Centers that consist of HTS-ready primary screening assays
  2. secondary hit validation assays and counter-screening assays used to test for probe attributes not identified in the primary screening assay.  These Centers are resourced to screen assays against a small molecule compound collection assembled for this purpose, the Molecular Libraries Small Molecule Repository (MLSMR). 
  3. The Centers then validate the small molecule “hits” identified in the screen
  4. collaborate with the assay provider to perform counter-screening
  5. and then apply computational and synthetic medicinal chemistry approaches to optimize promising hit structures.

The Assay Development for HTS Program described by PAR-08-024 provides the funding necessary to translate assays from the lab bench into formats that can be used by the MLSCN Centers, and thus acts to promote the first necessary step required for molecular probe development. 

It is expected that 40-50 assay development projects will be funded (for $8 million), in response to two receipt dates each year for the Assay Development for HTS Program.

Additional Information

  • Notice of Opportunity for Fast Track Entry of  Assay Projects for High Throughput Screening into the NIH Roadmap Molecular Libraries Probe Production Centers Network
    Release Date: May 11, 2011
    Announcement Number: NOT-RM-11-018
    Funding Contact: David Jett, Ph.D.

Links to the Roadmap Molecular Libraries and Blueprint for Neuroscience Research Initiatives 

NIH Blueprint
NIH Roadmap

 

Institute Contact to the Program:

David Jett, Ph.D.
Program Director
Office of Translational Research
NIH/NINDS
Neuroscience Center, Room 2177
6001 Executive Blvd. MSC 9527
Bethesda, Maryland 20892-9527
Email: dj140o@nih.gov

Last updated December 20, 2013