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 #
5U19CA052995-21
Application #
7618258
Study Section
Special Emphasis Panel (ZCA1-SRRB-K (J1))
Program Officer
Forry, Suzanne L
Project Start
1990-08-06
Project End
2011-04-30
Budget Start
2009-08-17
Budget End
2011-04-30
Support Year
21
Fiscal Year
2009
Total Cost
$1,064,087
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
Gaitonde, Supriya; De, Surya K; Tcherpakov, Marianna et al. (2009) BI-69A11-mediated inhibition of AKT leads to effective regression of xenograft melanoma. Pigment Cell Melanoma Res 22:187-95
Ihle, Nathan T; Lemos, Robert; Schwartz, David et al. (2009) Peroxisome proliferator-activated receptor gamma agonist pioglitazone prevents the hyperglycemia caused by phosphatidylinositol 3-kinase pathway inhibition by PX-866 without affecting antitumor activity. Mol Cancer Ther 8:94-100
Ihle, Nathan T; Lemos Jr, Robert; Wipf, Peter et al. (2009) Mutations in the phosphatidylinositol-3-kinase pathway predict for antitumor activity of the inhibitor PX-866 whereas oncogenic Ras is a dominant predictor for resistance. Cancer Res 69:143-50

Showing the most recent 10 out of 34 publications