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NIH: National Institute of Diabetes and Digestive and Kidney Diseases NIH: National Institute of Diabetes and Digestive and Kidney Diseases 75 years: 1950-2025 75 years: 1950-2025
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  4. Translational Research
  5. Hit to Lead

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.

Starting Points
  1. Disease
    Biology
  2. Unvalidated
    Target
    Target ID
    Putative
    Targets
  3. Nominated
    Target
    Assay Development
    Screenable
    Assays
  4. Hit
    Hit to Lead
    Lead Series
  5. Pre‑clinical
    Candidate
    Pre‑clinical
    Development
    Clinical
    Therapeutic
    Candidate
  6. Clinical
    Candidate
    Clinical
    Development
    Clinical Proof
    of Concept
  7. Licensing and
    Commercializa-
    tion Partners
    Market-ready
    Therapeutics
Outcomes and Resources

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)

Related Resources

Staff Contacts

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

Last Reviewed October 2024