Abstract:
:Protein phosphorylation is the major post-translational modification used by eukaryotic cells to control cellular signaling. Protein kinases have emerged as attractive drug targets because heightened protein kinase activity has been associated with several proliferative diseases, most notably cancer and restenosis. Until now, it has been very difficult to confirm the utility of protein kinases as inhibitor targets because very few small molecules that selectively inhibit one particular kinase are known. Discovery of highly specific kinase inhibitors has been slow because the protein family contains approximately 2000 members, all of which share a conserved active site fold. Recent work in several laboratories has sought to circumvent the problem of kinase structural degeneracy by engineering drug sensitivity into Src family tyrosine kinases and mitogen-activated protein kinases through site-directed mutagenesis. By introducing a unique non-naturally occurring amino acid into a conserved region of the enzyme's binding site, a target protein kinase can be rapidly sensitized to a small molecule. Introduction of the engineered kinase into a cell line or animal model should greatly expedite the investigation of protein kinase inhibition as a viable drug treatment. The purpose of this review is to summarize these recent advances in protein kinase drug sensitization.
journal_name
Pharmacol Therjournal_title
Pharmacology & therapeuticsauthors
Bishop AC,Shokat KMdoi
10.1016/s0163-7258(98)00060-6subject
Has Abstractpub_date
1999-05-01 00:00:00pages
337-46issue
2-3eissn
0163-7258issn
1879-016Xjournal_volume
82pub_type
杂志文章,评审abstract::Lungs have a complex structure composed of different cell types that form approximately 17 million airway branches of gas-delivering bronchioles connected to 500 million gas-exchanging alveoli. Airways and alveoli are lined by epithelial cells that display a low rate of turnover at steady-state, but can regenerate the...
journal_title:Pharmacology & therapeutics
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journal_title:Pharmacology & therapeutics
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journal_title:Pharmacology & therapeutics
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journal_title:Pharmacology & therapeutics
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journal_title:Pharmacology & therapeutics
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doi:10.1016/j.pharmthera.2004.02.003
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journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
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journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
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journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
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journal_title:Pharmacology & therapeutics
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journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
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journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2013.06.003
更新日期:2013-10-01 00:00:00
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journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
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更新日期:1997-10-01 00:00:00
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journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2014.05.008
更新日期:2014-11-01 00:00:00
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journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2007.03.006
更新日期:2007-06-01 00:00:00
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journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2018.09.003
更新日期:2019-02-01 00:00:00
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journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/0163-7258(94)90046-9
更新日期:1994-08-01 00:00:00
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journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2013.08.005
更新日期:2014-01-01 00:00:00
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journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2014.12.005
更新日期:2015-04-01 00:00:00
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journal_title:Pharmacology & therapeutics
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更新日期:2006-01-01 00:00:00
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journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2018.01.004
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journal_title:Pharmacology & therapeutics
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更新日期:1997-01-01 00:00:00
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journal_title:Pharmacology & therapeutics
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doi:10.1016/j.pharmthera.2005.04.011
更新日期:2006-11-01 00:00:00
abstract::Known treatments of type 2 diabetes mellitus have limitations such as weight gain, and hypoglycaemias. A new perspective is the use of incretin hormones and incretin enhancers. Incretins are defined as being responsible for the higher insulin release after an oral glucose load compared to an intravenous glucose load. ...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
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journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2007.08.003
更新日期:2007-12-01 00:00:00
abstract::gamma-Aminobutyric acid(A) (GABA(A)) receptors are ligand-gated ion channels that, predominantly, mediate inhibitory synaptic transmission in the CNS. These receptors are pentameric complexes that are comprised of subunits from several classes (alpha, beta, gamma, delta, ), with each class consisting of several isofor...
journal_title:Pharmacology & therapeutics
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doi:10.1016/j.pharmthera.2003.12.001
更新日期:2004-03-01 00:00:00
abstract::Recent evidence indicates that ethanol modulates the function of specific intracellular signaling cascades, including those that contain cyclic adenosine 3', 5'-monophosphate (cAMP)-dependent protein kinase A (PKA), protein kinase C (PKC), the tyrosine kinase Fyn, and phospholipase D (PLD). In some cases, the specific...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2005.07.004
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abstract::Stroke and myocardial infarction are among the most common causes of mortality and disability in the world. The ischemic injury underlying these illnesses is complex, involving intricate interplays among many biological functions including energy metabolism, vascular regulation, hemodynamics, oxidative stress, inflamm...
journal_title:Pharmacology & therapeutics
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doi:10.1016/j.pharmthera.2018.05.006
更新日期:2018-10-01 00:00:00
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journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2008.01.001
更新日期:2008-04-01 00:00:00
abstract::The small heat shock proteins (HSPs) HSP20, HSP27 and alphaB-crystallin are chaperone proteins that are abundantly expressed in smooth muscles are important modulators of muscle contraction, cell migration and cell survival. This review focuses on factors regulating expression of small HSPs in smooth muscle, signaling...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2008.04.005
更新日期:2008-07-01 00:00:00
abstract::Common arrhythmias, particularly atrial fibrillation (AF) and ventricular tachycardia/fibrillation (VT/VF) are a major public health concern. Classic antiarrhythmic (AA) drugs for AF are of limited effectiveness, and pose the risk of life-threatening VT/VF. For VT/VF, implantable cardiac defibrillators appear to be th...
journal_title:Pharmacology & therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.pharmthera.2011.03.003
更新日期:2011-11-01 00:00:00