Translational Research: Hit to Lead
Hit-to-lead research involves taking initial lead compounds or biologics and performing additional experiments to more fully validate the hits. This often involves activities such as re-synthesis of a small molecule or sequence verification of a biologic. Then, limited exploration of the structure activity relationships (SAR) of small molecules or structure function relationships (SFR) of proteins is conducted by testing candidates that are similar but not identical to the hits. Characterization of potential leads for off target activity or preliminary absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies are sometimes carried out at this stage.
Target AssayScreeningHits and
HitHit to LeadLead Series
NIH Funding Opportunities
- PAR-22-111, Early-Stage Preclinical Validation of Therapeutic Leads for Diseases of Interest to the NIDDK (R01 Clinical Trial Not Allowed) has expired. The NIDDK is still interested in supporting this type of translational science and another potential option is to apply to the Parent R01 NOFO (PA-20-185) and consider requesting review assignment to any of CSR’s Drug Synthesis, Discovery, Disposition, and Xenobiotics study sections, or another relevant review panel. Applicants should consult the NIH/CSR study section descriptions before requesting a specific review panel.
- RFA-NS-24-019, HEAL Initiative: Non-addictive Analgesic Therapeutics Development [Small Molecules and Biologics] to Treat Pain (UG3/UH3 Clinical Trial Optional)
- Academic Drug Discovery Consortium
- NIH Molecular Libraries and Imaging
- NIDDK Small Business Programs
Division of Kidney, Urologic, and Hematologic Diseases
Dr. Anna Sadusky
Division of Digestive Diseases and Nutrition
Dr. Bonnie Burgess-Beusse
Division of Diabetes, Endocrinology, and Metabolic Diseases
Dr. Yan Li