Discovery of in vivo Chemical Probes for the Nervous System

The Discovery of in vivo Chemical Probes for the Nervous System program is a federal funding opportunity administered by the National Institutes of Health within the U.S. Department of Health and Human Services, with participation from multiple institutes including the National Institute on Aging, National Eye Institute, National Institute on Drug Abuse, and National Institute of Mental Health. This program is structured as an R01 Research Project Grant and is designed to support advanced biomedical research focused on the development of chemical probes for studying biological processes in the nervous system. The initiative reflects NIH’s broader mission to expand scientific understanding of brain function, neurological diseases, and aging-related conditions through rigorous research and innovation. The primary purpose of this funding opportunity is to support investigators who already possess validated starting compounds and are prepared to conduct iterative optimization and testing to develop in vivo chemical probes. These probes are intended to modulate novel biological targets and enable deeper investigation into disease mechanisms. The program emphasizes discovery-oriented research rather than therapeutic development, and explicitly excludes projects focused on drug development or late-stage preclinical work. Funded research is expected to integrate chemistry and biology approaches, including structure-activity relationship studies, in vitro and in vivo assays, and pharmacokinetic and pharmacodynamic evaluations. Funding is provided through a grant mechanism with flexible budgeting, allowing applicants to request funds based on the actual needs of their proposed project. The maximum project period is five years, and there is no stated cap on award size. The program does not require cost sharing or matching funds. However, awardees must comply with NIH policies regarding allowable costs, reporting requirements, and data sharing. A Data Management and Sharing Plan is mandatory, and researchers are expected to deposit data such as assay results and chemical structures into public repositories like PubChem and the National Institute of Mental Health Data Archive. Eligibility for this opportunity is broad and includes higher education institutions, nonprofit organizations, for-profit entities including small businesses, and various levels of government organizations. Both domestic and international applicants are permitted, although foreign subawards are not allowed under this funding opportunity. Individuals serving as Program Directors or Principal Investigators must demonstrate the necessary expertise and must be affiliated with eligible organizations. Required registrations include SAM, Grants.gov, and eRA Commons, and applicants must ensure all systems are active prior to submission. The application process requires submission through approved NIH systems such as ASSIST or Grants.gov Workspace. Applicants must follow detailed instructions provided in the NIH Application Guide and include specific components such as a research strategy, validated hit compounds, assay descriptions, and a clear development pathway for chemical probes. Applications are evaluated through a peer review process based on scientific merit, innovation, feasibility, and the expertise of the research team. Additional considerations include data management, ethical compliance, and alignment with NIH priorities. The funding opportunity follows a recurring submission schedule with standard NIH due dates occurring multiple times per year. For the current cycle, applications open on May 5, 2026, with subsequent deadlines on June 5, October 5, and February 5 of the following year. Applications must be submitted by 5:00 PM local time on the due date. Review and award timelines are structured accordingly, with scientific review, advisory council review, and earliest start dates occurring several months after submission. The opportunity expires on March 6, 2027, but is expected to be reissued periodically. Applicants are encouraged to contact program staff at the participating NIH institutes for guidance and clarification during the application process. Multiple contact emails are provided for scientific, administrative, and submission-related inquiries. Overall, this funding opportunity represents a significant investment in foundational neuroscience research and offers substantial flexibility and support for investigators aiming to advance the discovery of novel biological insights through chemical probe development.

Ensure validated hit compounds are well-characterized; emphasize innovation and biological target significance; provide rigorous assay design and feasibility planning