This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The focus of our X-diffraction study is the cMet kinase-inhibitor complex. cMET and its ligand, hepatocyte growth factor/scatter factor have become one of the leading molecular targets in cancer. The success of targeting tyrosine kinase receptors in human cancer has triggered an entirely new therapeutic strategy for treating the disease. The project involves the development of drugs that might be of use in treating cancers. ArQule has several drugs in development that bind to specific protein receptors believed to be involved in cancers. This proposal is to examine the crystals structures of receptors-drug complexes in order to guide the stereo-synthesis of the drugs. In order to design a better inhibitor for cMet it is crucial to obtain the 3D-dimensional structure of its complex. We have generated crystals for complex of a small molecule inhibitors and cMet kinase. These crystals weakly diffract in our in-house X-ray source and difficult to determine the structure with a poor diffraction data. However, this problem could be solved by collecting diffraction data using an intense X-ray beam at BNL. A temporary access to BNL is crucial for us to conduct diffraction experiment on cMet-inhibitor complex.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
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Special Emphasis Panel (ZRG1-BCMB-R (40))
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Brookhaven National Laboratory
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