Funding Opportunity Number: PAR-24-088
Deadlines: November 5, 2024, February 5, 2025, March 5, 2025
Research Scope
Technological innovations in chemical synthesis, cheminformatics, structural biology, and high throughput bioactivity and drug property assays have allowed rapid discovery of novel, small-molecule probes for the study of disease-related biological processes and mechanisms in academic environments.
Through this Notice of Funding Opportunity (NOFO), NIMH, NIDA, NEI and/or NIA encourage applications to advance the discovery of small molecule chemical probes that would enable, by modulating the function of a novel biological target, mechanistic questions to be addressed in animal studies. The NIH aims to stimulate research in 1) discovery and development of a novel in vivo chemical probes for their potential use in understanding biological processes relevant to the missions of the participating NIH Institutes, and 2) use of chemical probes to discover and/or validate novel biological targets that will inform studies of brain disease mechanisms. Emphasis will be placed on research that provides new insight into important disease-related biological targets and biological processes. For example, applications may involve emerging therapeutic targets and mechanisms for the discovery of chemical probes that may lead to further development of therapeutics or provide insight into the biology of relevant diseases.
This program creates an opportunity for integrated research in biology and chemistry on structure-activity relationships (SAR) of novel compounds through an iterative and parallel optimization process, to advance the successful development of in vivo chemical probes. Applicants to this NOFO should have, in hand, the starting compounds ( validated hits ) for chemical optimization and bioassays for testing new analog compounds. The iterative bioassay and chemical optimization cycles may encompass:
- In vitro cellular and tissue activities (potency, selectivity assessment of on-target and off-target effects in cells, specificity, etc.).
- In vitro structural, physicochemical, and biochemical properties (solubility, stability, membrane permeability (Caco-2/MDR1-MDCK/PAMPA), protein binding, microsome stability, metabolite identification, CYP inhibition, etc.).
- In vivo pharmacokinetics (PK) with absorption, distribution, metabolism, excretion (ADME) and toxicity.
- In vivo efficacy.
The above-mentioned areas of investigation are representative and not meant to be all-inclusive.
The main emphasis of projects submitted under this NOFO should be on chemical probes development rather than drugs or therapeutic discovery, the latter of which are beyond the scope of this NOFO.
For more information, please see the opportunity webpage.