Recent advances in combinatorial chemistry together with the development of automated high-throughput screening devices offer enormous opportunity for identification of novel bioactive compounds. Chemical libraries that contain 20,000-100,000 stereochemically diverse compounds are already commercially, and the National Cancer Institute repositories contain vast numbers of cytotoxic compounds that remain uncharacterized. Finally, focused libraries will be generated in a sister core, Core D. A major limitation in the identification of useful compounds is the development of reliable bioassays and the ability to screening these libraries rapidly. Core C will focus on the development of methods for screening, and using these screens to assist COBRE investigators in identifying and characterizing useful compounds. Compounds that inhibit enzymes such as protein kinases, that bind cell receptors, or that inhibit biological processes by binding to previously unidentified molecules, can be identified with the use of high-throughput screens that will be implemented in Core C. Funds provided by the University and the State of Kansas will establish Core C infrastructure. Funds are requested from COBRE for the initial operation of Core C; including support for personnel and consumable supplies. This core will be supervised by experienced senior and junior COBRE program scientists with expertise in the areas of biochemistry, cell biology, molecular biology, and cancer research. The senior investigators will serve to advice and educate junior investigators regarding the utility of this core. The core will be directed by a senior investigator who is active in the development and use of novel bioassays for screening chemical libraries to identify novel anti-mitotic agents and new molecular targets for anti-cancer agents.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
1P20RR015563-01
Application #
6382805
Study Section
Special Emphasis Panel (ZRR1)
Project Start
2000-09-30
Project End
2005-08-31
Budget Start
Budget End
Support Year
1
Fiscal Year
2000
Total Cost
Indirect Cost
Name
University of Kansas Lawrence
Department
Type
DUNS #
072933393
City
Lawrence
State
KS
Country
United States
Zip Code
66045
Subramanian, Chitra; Grogan, Patrick T; Opipari, Valerie P et al. (2018) Novel natural withanolides induce apoptosis and inhibit migration of neuroblastoma cells through down regulation of N-myc and suppression of Akt/mTOR/NF-?B activation. Oncotarget 9:14509-14523
Ishiguro, Susumu; Kawabata, Atsushi; Zulbaran-Rojas, Alejandro et al. (2018) Co-treatment with a C1B5 peptide of protein kinase C? and a low dose of gemcitabine strongly attenuated pancreatic cancer growth in mice through T cell activation. Biochem Biophys Res Commun 495:962-968
He, Chenchen; Duan, Shaofeng; Dong, Liang et al. (2017) Characterization of a novel p110?-specific inhibitor BL140 that overcomes MDV3100-resistance in castration-resistant prostate cancer cells. Prostate 77:1187-1198
White, Peter T; Subramanian, Chitra; Zhu, Qing et al. (2016) Novel HSP90 inhibitors effectively target functions of thyroid cancer stem cell preventing migration and invasion. Surgery 159:142-51
Ohta, Naomi; Ishiguro, Susumu; Kawabata, Atsushi et al. (2015) Human umbilical cord matrix mesenchymal stem cells suppress the growth of breast cancer by expression of tumor suppressor genes. PLoS One 10:e0123756
Li, Benyi; Thrasher, James Brantley; Terranova, Paul (2015) Glycogen synthase kinase-3: a potential preventive target for prostate cancer management. Urol Oncol 33:456-63
Ishiguro, Susumu; Yoshimura, Kiyoshi; Tsunedomi, Ryouichi et al. (2015) Involvement of angiotensin II type 2 receptor (AT2R) signaling in human pancreatic ductal adenocarcinoma (PDAC): a novel AT2R agonist effectively attenuates growth of PDAC grafts in mice. Cancer Biol Ther 16:307-16
Li, Benyi; Sun, Aijing; Jiang, Wencong et al. (2014) PI-3 kinase p110?: a therapeutic target in advanced prostate cancers. Am J Clin Exp Urol 2:188-98
Bibis, Stergios S; Dahlstrom, Kelly; Zhu, Tongtong et al. (2014) Characterization of Leishmania major phosphatidylethanolamine methyltransferases LmjPEM1 and LmjPEM2 and their inhibition by choline analogs. Mol Biochem Parasitol 196:90-9
Subramanian, Chitra; Zhang, Huaping; Gallagher, Robert et al. (2014) Withanolides are potent novel targeted therapeutic agents against adrenocortical carcinomas. World J Surg 38:1343-52

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