The goals of this core are to evaluate AGT modulators in vivo for AGT- inactivating potency, therapeutic efficacy when combined with BCNU and rat pharmacokinetics. Compounds will be initially screened for AGT- inactivating potency in vitro and in cell culture as described in Core B of this application. Compounds from core B and ester prodrugs with tumor selectivity from Program 2 will be tested in Core C. Data generated from Core C will provide guidance on the further development of compounds in programs 2,3,4 and 5. In the initial year of funding, approximately 3 compounds will be evaluated/year for AGT inactivation and human tumor growth inhibition and 3-5 will be evaluated for rat pharmacokinetics. In the subsequent years of funding, an additional 2 compounds will be evaluated/year. The overall goal is to provide preclinical efficacy data to prioritize compounds with better therapeutic properties than O6- benzylguanine.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19CA057725-09
Application #
6347331
Study Section
Project Start
2000-09-30
Project End
2001-09-29
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
9
Fiscal Year
2000
Total Cost
$98,125
Indirect Cost
Name
Pennsylvania State University
Department
Type
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033