Opportunity Information: Apply for PAR 09 251
Apply for PAR 09 251
- The National Institutes of Health in the education health sector is offering a public funding opportunity titled "Optimization of Small Molecule Probes for the Nervous System (R21)" and is now available to receive applicants.
- Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.242 Mental Health Research Grants 93.273 Alcohol Research Programs 93.279 Drug Abuse and Addiction Research Programs 93.853 Extramural Research Programs in the Neurosciences and Neurological Disorders 93.866 Aging Research 93.867 Vision Research.
- This funding opportunity was created on Aug 13, 2009 and posted on Aug 13, 2009.
- Applicants must submit their applications by Sep 7, 2012. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
- Each selected applicant is eligible to receive up to $150,000.00 in funding.
- Eligible applicants include: City or township governments Private institutions of higher education Nonprofits having a 501(c)(3) status with the IRS, other than institutions of higher education Nonprofits that do not have a 501(c)(3) status with the IRS, other than institutions of higher education Native American tribal governments (Federally recognized) County governments Public and State controlled institutions of higher education Native American tribal organizations (other than Federally recognized tribal governments) Others (see text field entitled Additional Information on Eligibility for clarification) Special district governments Independent school districts For profit organizations other than small businesses State governments Small businesses Public housing authorities/Indian housing authorities.
- Other Eligible Applicants include the following Alaska Native and Native Hawaiian Serving Institutions Eligible Agencies of the Federal Government Faith based or Community based Organizations Hispanic serving Institutions Historically Black Colleges and Universities (HBCUs) Indian/Native American Tribal Governments (Other than Federally Recognized) Non domestic (non U.S.) Entities (Foreign Organizations) Regional Organizations Tribally Controlled Colleges and Universities (TCCUs) U.S. Territory or Possession.
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Opportunity Summary:
The NIH funding opportunity titled "Optimization of Small Molecule Probes for the Nervous System (R21)" (Funding Opportunity Number PAR 09-251) is an exploratory/developmental research grant aimed at helping investigators turn early small-molecule "hits" into well-characterized research probes that can be used to study biological function in the nervous system. The central idea is to support projects that sit at the intersection of medicinal chemistry and neuroscience-focused biology, where teams already have promising candidate compounds from screening efforts and now need resources to optimize those compounds into practical, reliable probes for downstream pharmacological and mechanistic studies.
This FOA is specifically geared toward applicants who have already done the upfront discovery work: they have screened small-molecule libraries or collections, built and used in vitro assays to identify active compounds, and have at least some evidence linking chemical structure to biological activity. In other words, the program is not mainly about starting from scratch with a brand-new target and an untested assay; it is about taking existing probe candidates and improving them through iterative chemistry and testing. A key expectation is that applicants will nominate probe candidates from distinct structural series (for example, more than one scaffold class) and then perform structured structure-activity relationship (SAR) studies, where analogs are designed, synthesized or acquired, and tested in cycles to understand what chemical changes improve or harm performance.
The work supported under this announcement emphasizes optimization using advanced medicinal chemistry paired with biological testing that is practical for medium-throughput workflows. The assays should be in vitro measures of biological function that can realistically be used repeatedly as analogs are generated, rather than one-off boutique experiments. The end goal is to produce a small-molecule probe with properties that make it genuinely useful in later studies proposed by the investigator, including the kinds of pharmacological experiments that require a compound to have credible affinity, selectivity, and functional activity. Although the FOA is about research probes rather than drug development per se, the attributes being optimized (such as potency and selectivity) mirror the standards needed for interpretable pharmacology in nervous system research.
An important practical element of the announcement is its encouragement to use publicly available cheminformatics resources to help with compound acquisition and the semi-custom synthesis of analogs. This reflects an interest in efficient, modern probe optimization approaches, including leveraging existing databases and toolkits to select analogs intelligently, source compounds, and plan synthesis in a way that accelerates SAR learning. The FOA frames this as a way to strengthen the chemistry-to-biology feedback loop and move from initial screening hits to probes that can be confidently used to interrogate nervous system biology.
The mechanism of support is the NIH R21, which is designed for exploratory and developmental projects. The announcement also notes that the National Institute of Neurological Disorders and Stroke (NINDS) anticipated releasing companion opportunities with the same scientific scope under small business mechanisms: SBIR (R43) and STTR (R41). That matters because it signals the program is open to similar probe-optimization work in both academic/nonprofit settings (via R21) and commercialization-oriented small business settings (via SBIR/STTR), even though this specific listing is for the R21 route.
Funding size and number of awards are not fixed in the text provided, and the FOA explicitly states that award size and duration may vary depending on the scope of the proposed research. The total number of awards and total dollars ultimately depend on the number of applications received and their overall quality, budgets, and timelines. The listing indicates an award ceiling of $150,000, while also emphasizing variability across projects, which is consistent with the R21 being used to support focused, early-stage optimization efforts rather than large-scale, multi-year development programs.
Eligibility is broad and includes a wide range of organization types: public and private institutions of higher education, nonprofit organizations (with and without 501(c)(3) status), for-profit organizations (other than small businesses), small businesses, and multiple levels of government (state, county, city/township, special district), among others. It also explicitly includes categories such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving institutions, tribally controlled colleges and universities, Alaska Native and Native Hawaiian serving institutions, faith-based and community-based organizations, U.S. territories/possessions, and even non-U.S. entities (foreign organizations), as well as eligible federal agencies and regional organizations. The opportunity does not require cost sharing or matching.
Administratively, the opportunity was posted and created on August 13, 2009, with a closing date of September 7, 2012, and it was archived on October 8, 2012. The sponsoring agency is the National Institutes of Health, and the program is associated with several CFDA numbers spanning mental health, alcohol research, drug abuse, neuroscience/neurological disorders, aging research, and vision research, which reflects the cross-cutting relevance of small-molecule probes across multiple NIH mission areas as long as the focus remains on nervous system biology and function.
In practical terms, the FOA is best read as support for projects that can clearly articulate: (1) what the probe candidates are and what structural series they represent, (2) what assay system(s) will be used for iterative testing in a medium-throughput manner, (3) what medicinal chemistry strategy will drive SAR learning and optimization, and (4) what performance characteristics will define success for the probe so it can be used in later pharmacological or mechanistic studies. The announcement is not simply funding "chemistry" or "biology" alone; it is funding the iterative loop between the two, with the explicit deliverable being an optimized small-molecule probe suitable for rigorous nervous system research.
Frequently Asked Questions (FAQs)
What is the purpose of this NIH funding opportunity?
This opportunity supports exploratory/developmental projects that take early small-molecule screening "hits" and optimize them into well-characterized research probes for studying biological function in the nervous system. The emphasis is on producing practical, reliable probes that can be used in later pharmacological and mechanistic studies.
What is the funding opportunity title and number?
The title is "Optimization of Small Molecule Probes for the Nervous System (R21)" and the Funding Opportunity Number is PAR 09-251.
What NIH grant mechanism is used?
The mechanism is the NIH R21, which is intended for exploratory and developmental research projects.
What types of projects are a good fit?
Projects are a good fit when investigators already have promising candidate compounds identified through screening and now need support to optimize those compounds via iterative medicinal chemistry and repeated biological testing. The program is designed for work at the intersection of medicinal chemistry and neuroscience-focused biology.
Is this program meant for brand-new targets and untested assays?
No. It is not mainly about starting from scratch with a new target and an untested assay. It is focused on improving existing probe candidates that already have evidence of biological activity and some structure-activity relationship (SAR) signal.
What prior work is expected before applying?
The FOA is geared toward applicants who have already conducted upfront discovery work, such as screening small-molecule libraries/collections, developing and using in vitro assays to find active compounds, and generating at least some evidence linking chemical structure to biological activity.
What is the role of structure-activity relationship (SAR) studies in this FOA?
SAR is central to the work supported. Applicants are expected to design, synthesize or acquire analogs, test them, and repeat this cycle to learn which chemical changes improve or degrade probe performance.
Do applicants need to propose more than one chemical series or scaffold?
Yes. A key expectation is that applicants will nominate probe candidates from distinct structural series (for example, more than one scaffold class) and then optimize them through structured SAR studies.
What kind of assays are expected for iterative testing?
The FOA emphasizes in vitro measures of biological function that are practical for medium-throughput workflows, meaning the assays should be feasible to run repeatedly as analogs are generated rather than being one-off, boutique experiments.
What is the main deliverable at the end of the project?
The intended deliverable is an optimized small-molecule probe with properties that make it genuinely useful for later nervous system studies proposed by the investigator, including pharmacological and mechanistic experiments.
Is this a drug development program?
No. The focus is on research probes rather than drug development. However, the attributes being optimized (such as potency and selectivity) are aligned with standards needed for interpretable pharmacology in nervous system research.
What probe characteristics are emphasized for optimization?
The FOA highlights improving characteristics that support rigorous downstream use, including credible affinity, selectivity, and functional activity, so the probe can be used confidently to interrogate nervous system biology.
How does the FOA describe the chemistry-to-biology workflow?
It is framed as an iterative loop between medicinal chemistry and biological testing, supported by repeated assay-driven feedback to accelerate learning and optimization from initial hits to reliable probes.
Does the FOA encourage the use of cheminformatics resources?
Yes. It encourages using publicly available cheminformatics resources to assist with compound acquisition and semi-custom synthesis of analogs, with the goal of making SAR cycles more efficient and accelerating optimization.
Can projects leverage existing compound sources rather than synthesizing everything?
Yes. The FOA explicitly discusses using resources to help with compound acquisition and semi-custom synthesis, reflecting an emphasis on efficient approaches to selecting, sourcing, and planning analog generation.
What is the award ceiling mentioned in the listing?
The listing indicates an award ceiling of $150,000, while also noting that award size and duration may vary depending on the scope of the proposed research.
Are the number of awards and total funding levels fixed?
No. The FOA states that the total number of awards and total dollars depend on the number of applications received and their quality, along with proposed budgets and timelines.
Does this opportunity require cost sharing or matching funds?
No. The opportunity does not require cost sharing or matching.
Who is eligible to apply?
Eligibility is broad and includes public and private institutions of higher education, nonprofit organizations (with and without 501(c)(3) status), for-profit organizations (other than small businesses), small businesses, and multiple levels of government (state, county, city/township, special district), among others.
Are minority-serving institutions and community-based organizations included in eligibility?
Yes. The FOA explicitly includes categories such as HBCUs, Hispanic-serving institutions, tribally controlled colleges and universities, Alaska Native and Native Hawaiian serving institutions, faith-based organizations, and community-based organizations.
Are foreign organizations eligible?
Yes. The FOA explicitly includes non-U.S. entities (foreign organizations) among eligible applicants.
Are U.S. territories and possessions eligible?
Yes. U.S. territories/possessions are explicitly included in the eligibility categories.
Which NIH institute is associated with the program scope mentioned?
The announcement notes that the National Institute of Neurological Disorders and Stroke (NINDS) anticipated releasing companion opportunities with the same scientific scope under small business mechanisms (SBIR/STTR).
Are there companion opportunities for small businesses mentioned?
Yes. The FOA notes anticipated companion opportunities with the same scientific scope under SBIR (R43) and STTR (R41), signaling that similar probe-optimization work may also be pursued through those mechanisms even though this specific listing is for the R21 route.
What are the key elements a strong application should articulate?
The FOA indicates projects should clearly describe (1) the probe candidates and the structural series they represent, (2) the assay system(s) for iterative, medium-throughput testing, (3) the medicinal chemistry strategy for driving SAR learning and optimization, and (4) the performance characteristics that will define success for downstream use.
What is the focus area for the biology component?
The biology focus is on nervous system biology and function, with in vitro functional assays used in a repeated, practical testing workflow to support optimization.
When was this opportunity posted and what are the key dates?
The opportunity was posted and created on August 13, 2009. The closing date was September 7, 2012, and it was archived on October 8, 2012.
Who is the sponsoring agency?
The sponsoring agency is the National Institutes of Health (NIH).
What CFDA program areas are associated with this FOA?
The FOA is associated with several CFDA numbers spanning mental health, alcohol research, drug abuse, neuroscience/neurological disorders, aging research, and vision research, reflecting cross-cutting relevance as long as the work focuses on nervous system biology and function.
Is the FOA funding "chemistry only" or "biology only" projects?
No. The FOA is explicitly about the iterative loop between medicinal chemistry and biological testing, with the deliverable being an optimized small-molecule probe suitable for rigorous nervous system research.
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| Optimization of Small Molecule Probes for the Nervous System (STTR R41) Apply for PAR 09 259 Funding Number: PAR 09 259 Agency: National Institutes of Health Category: Education Health Funding Amount: $150,000 |
| Optimization of Small Molecule Probes for the Nervous System (SBIR R43) Apply for PAR 09 260 Funding Number: PAR 09 260 Agency: National Institutes of Health Category: Education Health Funding Amount: $150,000 |
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| Community Networks Program (CNP) Centers for Reducing Cancer Disparities through Outreach, Research and Training (U54) Apply for RFA CA 09 032 Funding Number: RFA CA 09 032 Agency: National Institutes of Health Category: Education Health Funding Amount: $900,000 |
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