PMID- 18183025
OWN - NLM
STAT- MEDLINE
DCOM- 20080221
LR  - 20220318
IS  - 1546-1696 (Electronic)
IS  - 1087-0156 (Linking)
VI  - 26
IP  - 1
DP  - 2008 Jan
TI  - A quantitative analysis of kinase inhibitor selectivity.
PG  - 127-32
LID - 10.1038/nbt1358 [doi]
AB  - Kinase inhibitors are a new class of therapeutics with a propensity to inhibit 
      multiple targets. The biological consequences of multi-kinase activity are poorly 
      defined, and an important step toward understanding the relationship between 
      selectivity, efficacy and safety is the exploration of how inhibitors interact 
      with the human kinome. We present interaction maps for 38 kinase inhibitors 
      across a panel of 317 kinases representing >50% of the predicted human protein 
      kinome. The data constitute the most comprehensive study of kinase inhibitor 
      selectivity to date and reveal a wide diversity of interaction patterns. To 
      enable a global analysis of the results, we introduce the concept of a 
      selectivity score as a general tool to quantify and differentiate the observed 
      interaction patterns. We further investigate the impact of panel size and find 
      that small assay panels do not provide a robust measure of selectivity.
FAU - Karaman, Mazen W
AU  - Karaman MW
AD  - Ambit Biosciences, 4215 Sorrento Valley Blvd., San Diego, California 92121, USA.
FAU - Herrgard, Sanna
AU  - Herrgard S
FAU - Treiber, Daniel K
AU  - Treiber DK
FAU - Gallant, Paul
AU  - Gallant P
FAU - Atteridge, Corey E
AU  - Atteridge CE
FAU - Campbell, Brian T
AU  - Campbell BT
FAU - Chan, Katrina W
AU  - Chan KW
FAU - Ciceri, Pietro
AU  - Ciceri P
FAU - Davis, Mindy I
AU  - Davis MI
FAU - Edeen, Philip T
AU  - Edeen PT
FAU - Faraoni, Raffaella
AU  - Faraoni R
FAU - Floyd, Mark
AU  - Floyd M
FAU - Hunt, Jeremy P
AU  - Hunt JP
FAU - Lockhart, Daniel J
AU  - Lockhart DJ
FAU - Milanov, Zdravko V
AU  - Milanov ZV
FAU - Morrison, Michael J
AU  - Morrison MJ
FAU - Pallares, Gabriel
AU  - Pallares G
FAU - Patel, Hitesh K
AU  - Patel HK
FAU - Pritchard, Stephanie
AU  - Pritchard S
FAU - Wodicka, Lisa M
AU  - Wodicka LM
FAU - Zarrinkar, Patrick P
AU  - Zarrinkar PP
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Nat Biotechnol
JT  - Nature biotechnology
JID - 9604648
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Proteome)
RN  - EC 2.7.- (Phosphotransferases)
SB  - IM
MH  - Binding Sites
MH  - Enzyme Activation
MH  - Humans
MH  - Phosphotransferases/*antagonists & inhibitors
MH  - Protein Binding
MH  - Protein Interaction Mapping/*methods
MH  - Protein Kinase Inhibitors/*chemistry
MH  - Proteome/*chemistry
MH  - *Quantitative Structure-Activity Relationship
EDAT- 2008/01/10 09:00
MHDA- 2008/02/22 09:00
CRDT- 2008/01/10 09:00
PHST- 2007/07/19 00:00 [received]
PHST- 2007/11/08 00:00 [accepted]
PHST- 2008/01/10 09:00 [pubmed]
PHST- 2008/02/22 09:00 [medline]
PHST- 2008/01/10 09:00 [entrez]
AID - nbt1358 [pii]
AID - 10.1038/nbt1358 [doi]
PST - ppublish
SO  - Nat Biotechnol. 2008 Jan;26(1):127-32. doi: 10.1038/nbt1358.