Translational Research: Lead Optimization
Lead optimization is the process of generating a pre-therapeutic lead candidate by improving the properties of small molecules or non-viral biologics for which positive and negative attributes have been identified and candidates are tractable to modification. Examples of properties to be improved may be potency, efficacy, selectivity, or bioavailability. This process typically involves the generation and testing of multiple new agents in order to gain a scientific understanding of how variations in lead candidates effect these properties. It is expected that lead optimization will involve assessment of efficacy in animal models and/or ex vivo human samples.
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Disease
Biology -
Unvalidated
TargetTarget IDPutative
Targets -
Nominated
TargetAssay DevelopmentScreenable
Assays -
Target AssayScreeningHits and
Starting Points -
HitHit to LeadLead Series
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Lead
CompoundLead
OptimizationPotential
Therapeutic
Leads -
Pre‑clinical
CandidatePre‑clinical
DevelopmentClinical
Therapeutic
Candidate -
Clinical
CandidateClinical
DevelopmentClinical Proof
of Concept -
Licensing and
Commercializa-
tion PartnersMarket-ready
Therapeutics
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.
Related Resources
- Academic Drug Discovery Consortium
- NIH Molecular Libraries and Imaging
- NCATS TRND
- PubChem
- Medicinal Chemical Facilities
- NIDDK Small Business Programs
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