Abstract：
:Kinase-targeted therapy is a new and promising approach to disease treatment. However, some kinase inhibitors have been observed to cause an off-target adverse risk for skeletal system by influencing the growth of osteoblasts. It is known that the proliferation and differentiation of osteoblasts are essentially regulated by MAPK signaling pathway, and many off-target events are considered to influence this pathway. Here, the unexpected MAPK-inhibitor interactions in mouse MC3T3-E1 osteoblastic cells were investigated in detail using an integrative protocol. With bioinformatics analysis we successfully profiled a systematic noncognate interaction spectrum for off-target kinase inhibitors against mouse MAPK kinases, from which 13 potential MAPK-inhibitor interactions were identified. The inhibitors Nilotinib, Dasatinib and Bosutinib were suggested as promising candidates; their cytotoxicity on MC3T3-E1 and inhibitory activity against MAPK kinase were tested at cellular and molecular levels, respectively. We also tested two known MAPK inhibitors SP600125 and SB203580 as positive controls. Consequently, the Dasatinib was found to have high off-target risk for unexpectedly targeting osteoblast MAPK signaling pathway.
journal_name
Gen Physiol Biophysjournal_title
General physiology and biophysicsauthors
Zhao L,Huang Q,Tian S,Ge J,Zhu H,Dong Qdoi
10.4149/gpb_2018030subject
Has Abstractpub_date
2019-01-01 00:00:00pages
1-13issue
1eissn
0231-5882issn
1338-4325journal_volume
38pub_type
杂志文章abstract：:Elevated serum resistin is implicated in insulin resistance associated with obesity and type 2 diabetes mellitus. Alcohol consumption interferes with the nutritional status, metabolic and hormonal activity of the drinker. Impact of ethanol intake on resistin level and resistin metabolic effects is unknown. Effect of l...
journal_title：General physiology and biophysics
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journal_title：General physiology and biophysics
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journal_title：General physiology and biophysics
pub_type： 杂志文章
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abstract：:Phosphorylation of P-glycoprotein (PGP) by some protein kinases may play an important role in the regulation of its drug transport activity, and may also be important for the development of multidrug resistance (MDR) phenotype. In the present study we investigated the expression of three groups of mitogen-activated pr...
journal_title：General physiology and biophysics
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journal_title：General physiology and biophysics
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journal_title：General physiology and biophysics
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更新日期：1999-06-01 00:00:00
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journal_title：General physiology and biophysics
pub_type： 杂志文章
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journal_title：General physiology and biophysics
pub_type： 杂志文章
doi：10.4149/gpb_2009_02_140
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journal_title：General physiology and biophysics
pub_type： 杂志文章
doi：
更新日期：1990-06-01 00:00:00
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journal_title：General physiology and biophysics
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doi：
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journal_title：General physiology and biophysics
pub_type： 杂志文章
doi：
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journal_title：General physiology and biophysics
pub_type： 杂志文章
doi：
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journal_title：General physiology and biophysics
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journal_title：General physiology and biophysics
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更新日期：2012-09-01 00:00:00
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journal_title：General physiology and biophysics
pub_type： 杂志文章,评审
doi：
更新日期：2009-01-01 00:00:00
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journal_title：General physiology and biophysics
pub_type： 杂志文章
doi：
更新日期：2005-03-01 00:00:00
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journal_title：General physiology and biophysics
pub_type： 杂志文章
doi：
更新日期：1984-04-01 00:00:00
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journal_title：General physiology and biophysics
pub_type： 杂志文章,评审
doi：
更新日期：1996-10-01 00:00:00
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journal_title：General physiology and biophysics
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doi：
更新日期：1999-10-01 00:00:00
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更新日期：2009-01-01 00:00:00
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journal_title：General physiology and biophysics
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doi：
更新日期：2007-03-01 00:00:00
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journal_title：General physiology and biophysics
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doi：
更新日期：2009-01-01 00:00:00
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journal_title：General physiology and biophysics
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doi：
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journal_title：General physiology and biophysics
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doi：
更新日期：2007-06-01 00:00:00
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journal_title：General physiology and biophysics
pub_type： 杂志文章
doi：10.4149/gpb_2017021
更新日期：2018-01-01 00:00:00
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journal_title：General physiology and biophysics
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doi：
更新日期：2006-09-01 00:00:00
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journal_title：General physiology and biophysics
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更新日期：2010-03-01 00:00:00
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journal_title：General physiology and biophysics
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doi：
更新日期：1993-02-01 00:00:00
