Opportunity Information: Apply for RFA CA 23 028
This funding opportunity, titled "Discovery and Development of Natural Products for Cancer Interception and Prevention (UG3/UH3 Clinical Trial Not Allowed)" (RFA-CA-23-028), is a National Institutes of Health (NIH) cooperative agreement designed to push promising natural products toward practical use in cancer interception and prevention. The central aim is to support projects that identify and develop novel natural products that are safe, non-toxic, and effective in preventing cancer or stopping early disease processes before cancer becomes clinically apparent. The structure is milestone-driven and phased, meaning teams are expected to hit clear development benchmarks to move from early exploratory work into more advanced development activities.
The award uses the UG3/UH3 phased mechanism. The UG3 phase is the exploratory and preparatory stage, focused on choosing clinically relevant biological targets and building the tools needed to test natural products against those targets. In practical terms, applicants are expected to select targets that matter for interception or prevention and then develop, optimize, and validate assays that can reliably measure desired bioactivity. Just as importantly, UG3 activities also include establishing and validating toxicity screening approaches so that candidates can be filtered early for safety and tolerability. This phase is essentially about creating a rigorous screening and decision framework: targets that make clinical sense, assays that generate trustworthy data, and safety screens that prevent weak or risky candidates from moving forward.
The UH3 phase is the development stage that begins once UG3 milestones are met. UH3-supported work centers on screening natural product libraries using the validated assays, followed by the technical and scientific steps required to turn "hits" into well-characterized candidates. That includes structure elucidation (figuring out the chemical identity and structure of active compounds), full-scale characterization (deeper profiling of activity, selectivity, and properties), efficacy testing (demonstrating preventive or interception-relevant effects in appropriate models), and further development of the screened agents. In short, the UH3 phase is where discovery transitions into a more translational development pathway, with the expectation that candidates are not just interesting in a dish but are sufficiently defined and tested to justify continued advancement.
A key boundary of this announcement is that clinical trials are not allowed, which signals that NIH is aiming this program at preclinical discovery and development rather than human testing. Projects should therefore be built around laboratory, analytical, and preclinical efficacy and safety work that lays the groundwork for future clinical translation, without proposing interventional studies in human participants under this particular funding mechanism.
The opportunity falls under the "Discretionary" category and uses a "Cooperative Agreement" funding instrument, which generally implies substantial NIH involvement in stewardship, coordination, or scientific partnership compared with a standard grant. The activity category is listed under Education and Health, and the CFDA number provided is 93.393. The listing shows an award ceiling of $250,000, and the original closing date is 2025-06-13.
Eligibility is broad and includes many types of U.S.-based organizations and governmental entities. Eligible applicants include state, county, and city/township governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized tribal governments; public housing authorities/Indian housing authorities; tribal organizations that are not federally recognized governments; nonprofits with and without 501(c)(3) status (outside of higher education); for-profit organizations other than small businesses; small businesses; and other entities as allowed by NIH policy. The announcement also explicitly highlights additional eligible applicants such as Alaska Native and Native Hawaiian Serving Institutions; Asian American, Native American, and Pacific Islander Serving Institutions (AANAPISIs); Hispanic-serving institutions; Historically Black Colleges and Universities (HBCUs); Tribally Controlled Colleges and Universities (TCCUs); faith-based or community-based organizations; eligible federal agencies; regional organizations; and U.S. territories or possessions.
There are important limits on foreign participation. Non-domestic (non-U.S.) entities and non-domestic foreign institutions are not eligible to apply as the applicant organization, and non-domestic components of U.S. organizations are not eligible to apply. However, foreign components are allowed as defined in the NIH Grants Policy Statement, meaning a U.S.-based applicant may include certain foreign collaborations or elements if they meet NIH definitions and requirements.
Taken together, this program is aimed at teams capable of combining natural product discovery, modern assay development, toxicity screening, chemical structure work, and preclinical efficacy evaluation, all within a phased, milestone-based framework. The emphasis is on generating well-validated screening systems in UG3 and then using those systems in UH3 to identify, define, and develop natural product candidates with a credible path toward cancer interception and prevention, while stopping short of clinical trial activity under this specific announcement.Apply for RFA CA 23 028
- The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Discovery and Development of Natural Products for Cancer Interception and Prevention (UG3/UH3 Clinical Trial Not Allowed)" and is now available to receive applicants.
- Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.393.
- This funding opportunity was created on 2023-03-23.
- Applicants must submit their applications by 2025-06-13. (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 $250,000.00 in funding.
- Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), 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, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.
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Frequently Asked Questions (FAQs)
What is the title of this funding opportunity?
The opportunity is titled "Discovery and Development of Natural Products for Cancer Interception and Prevention (UG3/UH3 Clinical Trial Not Allowed)" and is identified as RFA-CA-23-028.
What agency is offering this program?
This is a National Institutes of Health (NIH) funding opportunity.
What is the main purpose of this award?
The goal is to support projects that identify and develop novel natural products that are safe, non-toxic, and effective for cancer interception and prevention. The program is designed to push promising natural products toward practical use by advancing them through a phased, milestone-driven preclinical development process.
What does "cancer interception and prevention" mean in the context of this announcement?
Within this announcement, projects should focus on preventing cancer or stopping early disease processes before cancer becomes clinically apparent, using natural product-based agents and preclinical evidence generation.
What funding mechanism is used (UG3/UH3)?
The award uses the UG3/UH3 phased mechanism. UG3 supports early exploratory and preparatory work, and UH3 supports the later development work once UG3 milestones are successfully met.
How does the milestone-driven, phased structure work?
Teams are expected to define and meet clear development benchmarks. Progress through the program is tied to achieving stated milestones in the UG3 phase before transitioning to the UH3 phase, where more advanced discovery-to-development activities occur.
What activities are expected in the UG3 phase?
The UG3 phase is focused on selecting clinically relevant biological targets for interception or prevention and building the testing framework needed to evaluate natural products against those targets. This includes developing, optimizing, and validating assays to measure desired bioactivity and establishing and validating toxicity screening approaches to filter candidates early for safety and tolerability.
Why is target selection emphasized in the UG3 phase?
The UG3 phase is intended to ensure the project is anchored in clinically relevant biology for cancer interception or prevention. The program description emphasizes choosing targets that "matter" for interception or prevention and building reliable tools to test natural products against those targets.
What does the opportunity mean by "assay development, optimization, and validation"?
It refers to building and refining test methods that can reliably measure whether a natural product has the desired biological activity against selected targets, and ensuring those methods generate trustworthy, reproducible data for screening and decision-making.
What role does toxicity screening play in this program?
Toxicity screening is a required component of the UG3-stage framework. The intent is to establish and validate approaches that identify safety or tolerability concerns early, preventing weak or risky candidates from moving forward into later development work.
What activities are expected in the UH3 phase?
UH3 begins after UG3 milestones are met and supports development work such as screening natural product libraries using validated assays, followed by steps to turn screening hits into well-characterized candidates. This includes structure elucidation, deeper characterization of activity and selectivity, efficacy testing in appropriate models, and further development of screened agents.
What is meant by "screening natural product libraries"?
It refers to testing collections of natural products using the validated assays established in UG3 to identify "hits" that show desired bioactivity and potential relevance to cancer interception or prevention.
What is "structure elucidation" in this context?
Structure elucidation means determining the chemical identity and structure of active compounds found through screening so that the candidate agents are sufficiently defined for further development and characterization.
What types of efficacy testing are anticipated?
The announcement indicates efficacy testing should demonstrate preventive or interception-relevant effects in appropriate models. The focus is preclinical, supporting a credible development pathway without proposing clinical trials.
Are clinical trials allowed under this funding opportunity?
No. Clinical trials are not allowed under this announcement. Projects should be built around laboratory, analytical, and preclinical efficacy and safety work rather than interventional studies in human participants.
If clinical trials are not allowed, what kind of work is appropriate?
Appropriate work includes preclinical discovery and development activities such as target selection, assay development and validation, toxicity screening, screening of natural product libraries, structure elucidation, candidate characterization, and preclinical efficacy evaluation in appropriate models.
What is the funding instrument type?
The listing describes this as a Cooperative Agreement.
What does a Cooperative Agreement imply for NIH involvement?
As described in the listing, a cooperative agreement generally implies substantial NIH involvement in stewardship, coordination, or scientific partnership compared with a standard grant.
What category is this opportunity listed under?
The opportunity is listed under the "Discretionary" category.
What activity category is associated with this listing?
The activity category is listed under Education and Health.
What is the CFDA number for this opportunity?
The CFDA number provided is 93.393.
What is the award ceiling shown in the listing?
The listing shows an award ceiling of $250,000.
What is the closing date for the opportunity?
The original closing date shown is 2025-06-13.
Who is eligible to apply?
Eligibility is broad for U.S.-based organizations and governmental entities. Eligible applicants include state, county, and city/township governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized tribal governments; public housing authorities/Indian housing authorities; tribal organizations that are not federally recognized governments; nonprofits with and without 501(c)(3) status (outside of higher education); for-profit organizations other than small businesses; small businesses; and other entities as allowed by NIH policy.
Does the announcement highlight any additional eligible institution types?
Yes. It explicitly highlights Alaska Native and Native Hawaiian Serving Institutions; Asian American, Native American, and Pacific Islander Serving Institutions (AANAPISIs); Hispanic-serving institutions; Historically Black Colleges and Universities (HBCUs); Tribally Controlled Colleges and Universities (TCCUs); faith-based or community-based organizations; eligible federal agencies; regional organizations; and U.S. territories or possessions.
Are non-U.S. (foreign) organizations eligible to apply as the applicant?
No. Non-domestic (non-U.S.) entities and non-domestic foreign institutions are not eligible to apply as the applicant organization under this opportunity.
Can a U.S. organization apply if it has non-domestic components?
Non-domestic components of U.S. organizations are not eligible to apply. However, the announcement notes that foreign components are allowed as defined in the NIH Grants Policy Statement, meaning a U.S.-based applicant may include certain foreign collaborations or elements if they meet NIH definitions and requirements.
What kinds of project teams does this program seem designed for?
Based on the description, the program is aimed at teams that can combine natural product discovery with modern assay development, toxicity screening, chemical structure work (including structure elucidation), and preclinical efficacy evaluation, operating within a phased and milestone-based framework.
What is the overall transition expected from UG3 to UH3?
UG3 is intended to create a rigorous screening and decision framework (clinically relevant targets, validated assays, validated toxicity screening). UH3 is intended to use that framework to screen libraries, identify hits, and advance them through characterization, structure elucidation, and preclinical efficacy-oriented development steps toward a more translational pathway, without entering clinical trials under this FOA.
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