Journal
FRONTIERS IN MOLECULAR BIOSCIENCES
Volume 2, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fmolb.2015.00027
Keywords
drug design; evolution; cancer drugs; protein kinases; conformational selection and induced fit; Gleevec
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Funding
- Howard Hughes Medical Institute
- Office of Basic Energy Sciences, CatalysisScience Program, U.S. Dept. of Energy [DE-FG02-05ER15699]
- NIH [GM100966-01]
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Sophisticated protein kinase networks, empowering complexity in higher organisms, are also drivers of devastating diseases such as cancer. Accordingly, these enzymes have become major drug targets of the twenty-first century. However, the holy grail of designing specific kinase inhibitors aimed at specific cancers has not been found. Can new approaches in cancer drug design help win the battle with this multi-faced and quickly evolving enemy? In this perspective we discuss new strategies and ideas that were born out of a recent breakthrough in understanding the molecular basis underlying the clinical success of the cancer drug Gleevec. An old method, stopped-flow kinetics, combined with old enzymes, the ancestors dating back up to about billion years, provides an unexpected outlook for future intelligent design of drugs.
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