Assay development and screening for discovery of chemical probes, drugs or immunomodulators (R01 Clinical Trial Not Allowed)

The National Cancer Institute (NCI) has launched a Notice of Funding Opportunity (NOFO) that focuses on the discovery of chemical probes, drugs, or immunomodulators. This initiative does not permit clinical trial studies. The research will strive to identify small molecules that can clarify the biology of disease, functioning as chemical probes or affecting disease targets for therapy or immunotherapy.

This funding opportunity aims to aid discovery research that identifies validated hits involving health outcomes of participating NIH Institutes. Four critical phases of discovery research are covered under this initiative.

The first phase demands the development of assays for precise biological targets and disease mechanisms pertaining to participating NIH Institutes. These assays will then be used to screen small molecule compounds showing potential as probes in advancing knowledge about known targets, discovering new targets, or as pre-therapeutic leads.

The second phase involves the implementation of high throughput target-focused approaches or moderate throughput phenotypic- and fragment-based approaches to recognize initial screening hits.

In the third phase, hit validation is key, which includes the application of secondary assays orthogonal to the primary assay, advanced cheminformatics analysis, and initial medicinal chemistry inspection. This aids in prioritizing the hit set and follow-up assays to determine the mode and mechanism of action of validated hits.

The final phase, hit-to-lead optimization, demands the use of Structure-Activity Relationship (SAR) to enhance target engagement, selectivity, and to lessen chemical liabilities. It also involves ADME (Absorption, Distribution, Metabolism, and Excretion), Pharmacokinetic (PK) and Pharmacodynamic (PD) studies, and in vivo modeling, if suitable, to test efficacy or biological effects.