Protein Kinase Inhibitors: Insights into Drug Design from Structure

@article{citeulike:325863, abstract = {Protein kinases are targets for treatment of a number of diseases. This review focuses on kinase inhibitors that are in the clinic or in clinical trials and for which structural information is available. Structures have informed drug design and have illuminated the mechanism of inhibition. We review progress with the receptor tyrosine kinases (growth factor receptors EGFR, VEGFR, and FGFR) and nonreceptor tyrosine kinases (Bcr-Abl), where advances have been made with cancer therapeutic agents such as Herceptin and Gleevec. Among the serine-threonine kinases, p38, Rho-kinase, cyclin-dependent kinases, and Chk1 have been targeted with productive results for inflammation and cancer. Structures have provided insights into targeting the inactive or active form of the kinase, for targeting the global constellation of residues at the ATP site or less conserved additional pockets or single residues, and into targeting noncatalytic domains.}, author = {Noble, Martin E. and Endicott, Jane A. and Johnson, Louise N. }, citeulike-article-id = {325863}, doi = {10.1126/science.1095920}, journal = {Science}, keywords = {chemical, inhibitor, kinase, review}, month = {March}, number = {5665}, pages = {1800--1805}, posted-at = {2006-05-28 16:51:18}, priority = {0}, title = {Protein Kinase Inhibitors: Insights into Drug Design from Structure}, url = {http://dx.doi.org/10.1126/science.1095920}, volume = {303}, year = {2004} }

TY - JOUR ID - citeulike:325863 L3 - citeulike-article-id:325863 TI - Protein Kinase Inhibitors: Insights into Drug Design from Structure JF - Science VL - 303 IS - 5665 SP - 1800 EP - 1805 N2 - Protein kinases are targets for treatment of a number of diseases. This review focuses on kinase inhibitors that are in the clinic or in clinical trials and for which structural information is available. Structures have informed drug design and have illuminated the mechanism of inhibition. We review progress with the receptor tyrosine kinases (growth factor receptors EGFR, VEGFR, and FGFR) and nonreceptor tyrosine kinases (Bcr-Abl), where advances have been made with cancer therapeutic agents such as Herceptin and Gleevec. Among the serine-threonine kinases, p38, Rho-kinase, cyclin-dependent kinases, and Chk1 have been targeted with productive results for inflammation and cancer. Structures have provided insights into targeting the inactive or active form of the kinase, for targeting the global constellation of residues at the ATP site or less conserved additional pockets or single residues, and into targeting noncatalytic domains. KW - chemical KW - inhibitor KW - kinase KW - review AU - Noble, Martin AU - Endicott, Jane AU - Johnson, Louise PY - 2004/03/19/ UR - http://dx.doi.org/10.1126/science.1095920 ER -