Notice of Intent to Publish a Funding Opportunity Announcement to Solicit Assays for High Throughput Screening (HTS) to Discover Chemical Probes (R21)

Notice Number: NOT-MH-12-007

Key Dates
Release Date: November 9, 2011

Issued by
National Institute of Mental Health (NIMH)


The National Institute of Mental Health (NIMH), in conjunction with the NIH Molecular Libraries Program and other participating NIH Institutes, intends to issue a Funding Opportunity Announcement (FOA) to encourage investigators to form collaborations with an established academic, nonprofit, or commercial HTS screening facility that has the requisite expertise and experience to implement HTS-ready assays for the discovery and development of small molecule chemical probes.

Through this planned FOA, NIH wishes to stimulate research in 1) discovery and development of novel, small molecules for their potential use in studying disease treatment relevant to the missions of the participating NIH Institutes, and 2) discovery and/or validation of novel, biological targets that will inform studies of disease mechanisms.  Emphasis will be placed on assays that provide new insight into important disease targets and processes.  

This FOA plans to utilize the NIH Exploratory/Developmental Grant (R21) award mechanism.  The FOA is expected to be published in December 2011 with the first receipt date planned for February 2012.

Research Initiative Details

This program intends to support mainly the following two stages of discovery research:

  1. HTS implementation. The screening facility should have the capability to optimize and automate biochemical-, cellular-, or whole organism-based assays to screen a large library of compounds with adequate diversity and representation of chemical space. The projects are expected to have ready an implementable HTS assay and a large collection of compounds to be screened. Some assay adaptation may be performed with the aim of optimizing parameters such as reagent preparation/consumption, assay readout, and automation in parallel or multiplex screening format. Such adaptation work will be accomplished through a joint effort between the assay submitting investigator and the screening facility responsible for implementing the assays. Some complementary research including biology-oriented chemical synthesis of screening compounds and virtual screening may also be conducted to improve the screening success likelihood.
  1. Hit validation. When HTS is complete, fresh samples of initial hit compounds will be selected (cherry-picked) for further confirmation. The investigators will implement secondary assays that are orthogonal to the primary assay to remove false positives. This provides additional verification that the hits are acting on the target/pathway of interest. In addition, the investigators will conduct advanced cheminformatics analysis and medicinal chemistry inspection to prioritize the hit set. It is expected that the investigators will test powder samples of hit compounds and commercially available analog compounds during the hit validation stage. Investigators should verify the structure of hits using a combination of analytical methods and, if possible, re-synthesis of select hits. Additional follow-up assays may also be conducted to characterize mode and mechanism of action of the validated hits.



Inquiries regarding this Notice may be directed to:

Yong Yao, Ph.D.
National Institute of Mental Health (NIMH)
NIH Molecular Libraries Initiative
Telephone:  301-443-6102

Weekly TOC for this Announcement
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