TY - JOUR
T1 - Allo-network drugs
T2 - Harnessing allostery in cellular networks
AU - Nussinov, Ruth
AU - Tsai, Chung Jung
AU - Csermely, Peter
N1 - Funding Information:
This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health (NIH), under contract number HHSN261200800001E, by the European Commission (FP6-518230; TÁMOP-4.2.2/B-10/1-2010-0013) and the Hungarian National Science Foundation (OTKA K69105 and K83314). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported (in part) by the Intramural Research Program of the NIH National Cancer Institute, Center for Cancer Research.
PY - 2011/12
Y1 - 2011/12
N2 - Allosteric drugs are increasingly used because they produce fewer side effects. Allosteric signal propagation does not stop at the 'end' of a protein, but may be dynamically transmitted across the cell. We propose here that the concept of allosteric drugs can be broadened to 'allo-network drugs' - whose effects can propagate either within a protein, or across several proteins, to enhance or inhibit specific interactions along a pathway. We posit that current allosteric drugs are a special case of allo-network drugs, and suggest that allo-network drugs can achieve specific, limited changes at the systems level, and in this way can achieve fewer side effects and lower toxicity. Finally, we propose steps and methods to identify allo-network drug targets and sites that outline a new paradigm in systems-based drug design.
AB - Allosteric drugs are increasingly used because they produce fewer side effects. Allosteric signal propagation does not stop at the 'end' of a protein, but may be dynamically transmitted across the cell. We propose here that the concept of allosteric drugs can be broadened to 'allo-network drugs' - whose effects can propagate either within a protein, or across several proteins, to enhance or inhibit specific interactions along a pathway. We posit that current allosteric drugs are a special case of allo-network drugs, and suggest that allo-network drugs can achieve specific, limited changes at the systems level, and in this way can achieve fewer side effects and lower toxicity. Finally, we propose steps and methods to identify allo-network drug targets and sites that outline a new paradigm in systems-based drug design.
UR - http://www.scopus.com/inward/record.url?scp=81755184126&partnerID=8YFLogxK
U2 - 10.1016/j.tips.2011.08.004
DO - 10.1016/j.tips.2011.08.004
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.systematicreview???
AN - SCOPUS:81755184126
SN - 0165-6147
VL - 32
SP - 686
EP - 693
JO - Trends in Pharmacological Sciences
JF - Trends in Pharmacological Sciences
IS - 12
ER -
