The National Cancer Institute (NCI) is accepting applications to create multidisciplinary research groups or partnerships for the discovery of pharmacological agents to treat fusion oncoprotein-driven childhood cancers. Details k first para s ye hatana UM1 Technology,
Donor Name: National Institutes of Health (NIH)
State: All States
County: All Counties
U.S. Territory: American Samoa, Guam, Commonwealth of Puerto Rico, Commonwealth of Northern Mariana Islands, U.S. Virgin Islands
Type of Grant: Grant
Deadline: 10/15/2023
Size of the Grant: not exceed $1.5 million
Grant Duration: 5 years
Details:
This NOFO will use the UM1 mechanism to fund Next Generation Chemistry (NGC) Centers with interdisciplinary teams focusing on innovative medicinal chemistry, chemical biology and chemoproteomic approaches to target fusion oncoprotein-driven cancers. The goal of this program is to accelerate innovative drug discovery focused on developing small molecules to effectively disrupt fusion oncoproteins through mechanisms including, but not limited to, inhibiting activities of fusion oncoproteins, blocking critical fusion oncoprotein interactions, modulating coding and/or noncoding RNAs required for fusion protein oncogenesis, and selectively degrading fusion proteins and/or proteins representing critical fusion oncoprotein dependencies. The NCI encourages applications to advance the discovery, preclinical development, and proof of concept testing of new, rationally designed candidate agents to treat fusion-derived childhood cancers. Funding priority will be given to applications that focus on fusion oncoproteins found in tumors that have high risk of treatment failure and for which there has been little progress in identifying targeted therapeutic agents. Applications focused on pediatric solid tumors and brain tumors are particularly encouraged. Small molecules are defined here as chemically synthesized drug-like compounds with molecular weights <2000 Da that can cross cell membranes to modulate fusion-oncoprotein functions.
The goal is to establish NGC Centers for Fusion Oncoproteins. Each NGC Center application should contain collaborative research projects by a multidisciplinary group of investigators focused on the discovery and development of small molecules to target fusion oncoprotein-driven pediatric cancers. Successful applicants will work within the context of a collaborative research network, the TFCC Network, to accelerate innovative drug discovery and preclinical development of therapeutics for fusion oncoprotein-driven childhood cancers. Each NGC Center will address discrete, relevant research opportunities pertaining to the development of novel pharmacologic agents for the treatment of one or more fusion oncoprotein-driven pediatric cancers. The NGC Center is expected to have capabilities that encompass relevant aspects of preclinical drug development and biological testing.
Applications focusing on fusion oncoproteins found in tumors that have high risk of treatment failure and for which there has been little progress in identifying targeted agents are strongly encouraged. As such, fusion oncoprotein targets for which clinical proof of concept has been achieved will be excluded from eligibility. Applications focused on pediatric solid tumors and brain cancers are particularly encouraged.
Potential areas of investigation depending upon project scope include, but are not limited to:
- Discovery and preclinical testing of novel compounds for fusion oncoprotein-driven pediatric cancers;
- Identifying and developing small molecules to effectively modulate the activities of individual fusion oncoproteins, block critical fusion protein interactions, interact with coding and/or noncoding RNAs required for fusion protein oncogenesis, or selectively lead to fusion protein degradation;
- Utilization of novel approaches such as chemoproteomics to discover and validate novel drug candidates, including targeted protein degraders;
- Computer-aided drug discovery to allow structure-based drug design;
- Development and validation of novel, fusion oncoprotein-based functional assays for evaluating therapeutic compounds. Measures with potential translational utility are particularly encouraged; and
- Initial Good Laboratory Practice (GLP) toxicology, safety pharmacology, and pharmacokinetics to support an investigational new drug (IND) application.
To properly address the NOFO goals, each proposed NGC Center will be expected to include diverse areas of expertise to facilitate progression from structure-function biochemical data to small molecule drug candidates and setting the stage for preclinical in vivo testing. Relevant areas of expertise that could be included are (among others) chemoproteomics, structural biology, molecular biology, medicinal chemistry, and experimental therapeutics. Multi-institutional collaborations are strongly encouraged to achieve the breadth of expertise required for a comprehensive approach to developing effective therapeutic agents for fusion oncoprotein-derived pediatric cancers. An NGC Center can focus on one or more potential target(s), as appropriate for the proposed scope and budget.
The overarching goal of the NGC Center program is to accelerate the development of novel small molecule therapeutic agents to treat fusion oncoprotein-derived childhood cancers. Each proposed Center is to consist of a multidisciplinary group of investigators with complementary skills that is committed to working together to achieve this goal. The overall structure of the Center is intended to facilitate coordinated and efficient drug discovery and development to produce potential therapeutic agents for recalcitrant fusion oncoprotein-driven pediatric cancers. The Center must include i) a Center Leadership Group (CLG), ii) up to four Research Groups, and iii) an Administrative Group (AG). These functional areas will be integrally connected to all aspects of the research agenda for developing potential therapeutics for fusion oncoprotein-driven childhood cancers.
Funding Information
Application budgets may not exceed $1.5 million in direct costs (excluding sub-award F&A costs) per year and must reflect the actual needs of the proposed project.
Project Period
The scope of the proposed project should determine the project period. The maximum project period is 5 years.
Eligible Organizations
Higher Education Institutions
- Public/State Controlled Institutions of Higher Education
- Private Institutions of Higher Education
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
- Hispanic-serving Institutions
- Historically Black Colleges and Universities (HBCUs)
- Tribally Controlled Colleges and Universities (TCCUs)
- Alaska Native and Native Hawaiian Serving Institutions
- Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)
Nonprofits Other Than Institutions of Higher Education
- Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
- Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
For-Profit Organizations
- Small Businesses
- For-Profit Organizations (Other than Small Businesses)
Local Governments
- State Governments
- County Governments
- City or Township Governments
- Special District Governments
- Indian/Native American Tribal Governments (Federally Recognized)
- Indian/Native American Tribal Governments (Other than Federally Recognized)
Federal Government
- Eligible Agencies of the Federal Government
- U.S. Territory or Possession
Other
- Independent School Districts
- Public Housing Authorities/Indian Housing Authorities
- Native American Tribal Organizations (other than Federally recognized tribal governments)
- Faith-based or Community-based Organizations
- Regional Organizations
Foreign Institutions
- Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
- Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
- Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
For more information, visit Grants.gov.