A Small Molecule Kinase Interaction Map for Clinical Kinase Inhibitors  

Oleh:

Floyd, Mark ; Fabian, Miles A. ; Biggs, William H. ; Treiber, Daniel K. ; Atteridge, Corey E. ; Azimioara, Mihai D. ; Benedetti, Michael G. ; Carter, Todd A. ; Ciceri, Pietro ; Edeen, Philip T. ; Ford, Julia M. ; Galvin, Margaret ; Gerlach, Jay L. ; Grotzfeld, Robert M. ; Herrgard, Sanna ; Insko, Darren E. ; Insko, Michael A. ; Lai, Andiliy G. ; Lelias, Jean-Michel ; Mehta, Shamal A. ; Milanov, Zdravko V. ; Velasco, Anne Marie ; Wodicka, Lisa M. ; Patel, Hitesh K. ; Zarrinkar, Patrick P. ; Lockhart, David J.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Nature Biotechnology: The Science and Business of Biotechnology vol. 23 no. 3 (Mar. 2005), page 329-336.
Topik: MOLECULE; small molecule; kinase interaction; clinical kinase inhibitors

Ketersediaan

Perpustakaan Pusat (Semanggi) Nomor Panggil: NN9.2 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

Lihat Detail Induk

Isi artikel

Kinase inhibitos show great promise as a new class of therapeutics. Here we describe an efficient way to determine kinase inhibitor specificity by measuring binding of small molecules to the ATP site of kinases. We have profiled 20 kinase inhibitors, including 16 that are approved drugs or in clinical development, against a panel of 119 protein kinases. We find that specificity varies widely and is not strongly correlated with chemical stucture or the identity of the intended target. Many novel interactions were identified including tight binding of the p38 inhibitor BIRB-796 to an imatinib resistant variant of the ABL kinase, and binding of imatinib to the SRC family kinase LCK. We also show that mutation in the epidermal growth factor receptor (EGFR) found in gefitinib responsive patients do not affect the binding affinity of gefitinib or erlotinib. Our results represent a systematic small molecule protein interation map for clinical compounds across a large number of related proteins.

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