The following are the objectives of Core B at The Ohio State University (OSU): (1) Synthesize sufficient quantities of selected natural products for more extensive biological evaluation, (2) Explore structure-activity relationships (SAR) and optimize pharmacological properties of highly promising agents through systematic modification of the natural product scaffold. All new compounds synthesized in these studies will be submitted for the bioassays proposed in Projects 1 and 3 and Core A, (3) Support the structural assignment of isolated natural products through chemical synthesis and/or semi-synthetic derivatization, as necessary, (4) Develop sensitive, selective, accurate and precise assays to quantify lead compounds in in vitro and in vivo biological matrices, (5) Characterize solubility, stability and metabolic profiles of lead compounds in dosing formulations and in vitro cell and enzyme preparations to support optimal formulation and derivatization, as necessary, and (6) Produce pilot plasma concentration-time profiles and determine protein and blood cell binding in mice for early estimation of pharmacokinetic properties for select compounds prior to entry into hollow fiber assays.

Public Health Relevance

The primary goal of Core B is to support the discovery, characterization and optimization of novel anticancer agents through the synthesis, structural modification, and evaluation of pharmacokinetic properties of lead compounds discovered in Projects 1-3 that demonstrate promising biological activity.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
2P01CA125066-06A1
Application #
8608731
Study Section
Special Emphasis Panel (ZCA1-RPRB-C (O1))
Project Start
2006-12-01
Project End
2019-04-30
Budget Start
2014-06-06
Budget End
2015-04-30
Support Year
6
Fiscal Year
2014
Total Cost
$135,485
Indirect Cost
Name
Ohio State University
Department
Type
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
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