Forecast for Expanding the Target Landscape by Drugging the Undruggable (R21 Clinical Trial Not Allowed)

The National Institutes of Health (NIH), through its National Center for Advancing Translational Sciences and in collaboration with other NIH Institutes and Centers, has released a forecast for an upcoming Notice of Funding Opportunity (NOFO) titled "Expanding the Target Landscape by Drugging the Undruggable." This grant aims to fund innovative research projects that focus on traditionally undruggable target classes associated with intractable human diseases. The intent is to stimulate the development of selective methods or agents that can effectively modulate these targets, which cannot be addressed by established therapeutic methods. The purpose of the funding is to support research that goes beyond conventional therapeutic approaches—such as those involving small molecules and biologics—to tackle targets considered undruggable, such as intrinsically disordered proteins, RNA, organelles, and metabolites. Projects funded under this NOFO should demonstrate a viable proof of concept, both in terms of modulating specific undruggable targets and in paving the way for broader application across the entire target class. The R21 activity code will be used for this opportunity, and clinical trials are not allowed. Eligible applicants include a wide range of organizations, such as public and state-controlled institutions of higher education, private higher education institutions, nonprofits with 501(c)(3) status, small and other for-profit businesses, independent school districts, county governments, tribal governments and organizations, and public housing authorities. The announcement encourages collaborative investigations, particularly those combining expertise in translational science, drug development, and drug discovery. The forecasted opportunity is expected to be formally posted on August 15, 2025, with an estimated application due date of October 16, 2025. Award notifications are anticipated by July 16, 2026, which is also the projected project start date. The estimated total program funding is $1,000,000, and three awards are expected to be made. No cost sharing or matching is required for this grant. At this time, applications are not being accepted. The current publication serves as an advance notice to allow interested researchers sufficient time to prepare collaborative, innovative proposals. For further details or inquiries, interested parties can contact Dr. Karlie Sharma at the National Center for Advancing Translational Sciences via email at Karlie.sharma@nih.gov or phone at 240-381-3118.