Abstract

The scope of this Core is to provide unique and innovative capabilities for the design and highaffinity, selective and drug-like compounds against the proposed targets. Bridging several disciplines within our NCDDG program, and collaborating closely with Projects 1 to 4 and the Chemistry Core, we will bring unique capabilities to the lead identification and optimization processes by combining structure-based design and our innovative NMR-based techniques, The specific tasks can be summarized as follows: 1) to provide support to Projects 1 to 4 in the identification of lead compounds by using molecular modeling and NMR-based techniques; 2) to provide support to Projects 1 to 4, in close collaboration with the Chemistry Core, to design optimized, high-affinity, selective and drug-like compounds by using a combination of molecular modeling and NMR-based straegies. ? ? Given our demonstrated experience with the proposed approaches and the synergy with Projects 1 to 4 and the Chemistry Core, we are confident that our efforts wil result in the identification of several lead compounds for all the proposed targets. ? ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19CA052995-19
Application #
7234710
Study Section
Special Emphasis Panel (ZCA1-SRRB-K (J1))
Program Officer
Forry, Suzanne L
Project Start
1990-08-06
Project End
2010-04-30
Budget Start
2007-05-01
Budget End
2008-04-30
Support Year
19
Fiscal Year
2007
Total Cost
$1,019,295
Indirect Cost

  Institution

Name
University of Texas MD Anderson Cancer Center
Department
Miscellaneous
Type
Other Domestic Higher Education
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030

  Publications

Ihle, N T; Powis, G; Kopetz, S (2011) PI-3-Kinase inhibitors in colorectal cancer. Curr Cancer Drug Targets 11:190-8
Liu, Enbo; Knutzen, Christine A; Krauss, Sybille et al. (2011) Control of mTORC1 signaling by the Opitz syndrome protein MID1. Proc Natl Acad Sci U S A 108:8680-5
Gwak, Ho-Shin; Shingu, Takashi; Chumbalkar, Vaibhav et al. (2011) Combined action of the dinuclear platinum compound BBR3610 with the PI3-K inhibitor PX-866 in glioblastoma. Int J Cancer 128:787-96
Leone, Marilisa; Barile, Elisa; Vazquez, Jesus et al. (2010) NMR-based design and evaluation of novel bidentate inhibitors of the protein tyrosine phosphatase YopH. Chem Biol Drug Des 76:10-6
Ihle, Nathan T; Powis, Garth (2010) The biological effects of isoform-specific PI3-kinase inhibition. Curr Opin Drug Discov Devel 13:41-9
Koul, Dimpy; Shen, Ruijun; Kim, Yong-Wan et al. (2010) Cellular and in vivo activity of a novel PI3K inhibitor, PX-866, against human glioblastoma. Neuro Oncol 12:559-69
Ihle, Nathan T; Powis, Garth (2010) Inhibitors of phosphatidylinositol-3-kinase in cancer therapy. Mol Aspects Med 31:135-44
Katiyar, Samiksha; Liu, Enbo; Knutzen, Christine A et al. (2009) REDD1, an inhibitor of mTOR signalling, is regulated by the CUL4A-DDB1 ubiquitin ligase. EMBO Rep 10:866-72
Molina, Gabriela; Vogt, Andreas; Bakan, Ahmet et al. (2009) Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages. Nat Chem Biol 5:680-7
Ihle, Nathan T; Powis, Garth (2009) Take your PIK: phosphatidylinositol 3-kinase inhibitors race through the clinic and toward cancer therapy. Mol Cancer Ther 8:1-9

Showing the most recent 10 out of 34 publications