Discovery and Development of Natural Products for Cancer Interception and Prevention (UG3/UH3 Clinical Trial Not Allowed) | RFA CA 23 028

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.

• 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.

Apply for RFA CA 23 028

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