Abstract

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. Mutational activation of EGFR kinase is an important cause of human non-small cell lung cancer (NSCLC). Small molecule drugs, Iressa and Tarceva, are effective in treating the disease caused by some types of the EGFR mutations, but the duration of efficacy is limited due to the emergence of a new mutation T790M in the EGFR kinase that confers resistance to the current drugs. We have identified several new compounds that can specifically inhibit EGFR kinase bearing the T790M mutation. There is a good chance that these new compounds can be used to treat the drug-resistant NSCLC after optimization. In this subproject we aim to solve the drugresistant EGFR mutant kinase in complex with these new compounds. This study will form the basis for optimization of these compounds.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR015301-09
Application #
8361664
Study Section
Special Emphasis Panel (ZRG1-BCMB-K (40))
Project Start
2011-04-01
Project End
2012-03-31
Budget Start
2011-04-01
Budget End
2012-03-31
Support Year
9
Fiscal Year
2011
Total Cost
$18,283
Indirect Cost

  Institution

Name
Cornell University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850

  Publications

Chen, Wenyang; Mandali, Sridhar; Hancock, Stephen P et al. (2018) Multiple serine transposase dimers assemble the transposon-end synaptic complex during IS607-family transposition. Elife 7:
Eichhorn, Catherine D; Yang, Yuan; Repeta, Lucas et al. (2018) Structural basis for recognition of human 7SK long noncoding RNA by the La-related protein Larp7. Proc Natl Acad Sci U S A 115:E6457-E6466
Fallas, Jorge A; Ueda, George; Sheffler, William et al. (2017) Computational design of self-assembling cyclic protein homo-oligomers. Nat Chem 9:353-360
Krotee, Pascal; Rodriguez, Jose A; Sawaya, Michael R et al. (2017) Atomic structures of fibrillar segments of hIAPP suggest tightly mated ?-sheets are important for cytotoxicity. Elife 6:
Dhayalan, Balamurugan; Mandal, Kalyaneswar; Rege, Nischay et al. (2017) Scope and Limitations of Fmoc Chemistry SPPS-Based Approaches to the Total Synthesis of Insulin Lispro via Ester Insulin. Chemistry 23:1709-1716
Uppalapati, Maruti; Lee, Dong Jun; Mandal, Kalyaneswar et al. (2016) A Potent d-Protein Antagonist of VEGF-A is Nonimmunogenic, Metabolically Stable, and Longer-Circulating in Vivo. ACS Chem Biol 11:1058-65
Mandal, Kalyaneswar; Dhayalan, Balamurugan; Avital-Shmilovici, Michal et al. (2016) Crystallization of Enantiomerically Pure Proteins from Quasi-Racemic Mixtures: Structure Determination by X-Ray Diffraction of Isotope-Labeled Ester Insulin and Human Insulin. Chembiochem 17:421-5
Dhayalan, Balamurugan; Fitzpatrick, Ann; Mandal, Kalyaneswar et al. (2016) Efficient Total Chemical Synthesis of (13) C=(18) O Isotopomers of Human Insulin for Isotope-Edited FTIR. Chembiochem 17:415-20
Ardiccioni, Chiara; Clarke, Oliver B; Tomasek, David et al. (2016) Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis. Nat Commun 7:10175
Bale, Jacob B; Gonen, Shane; Liu, Yuxi et al. (2016) Accurate design of megadalton-scale two-component icosahedral protein complexes. Science 353:389-94

Showing the most recent 10 out of 407 publications