Substituted indolin-2-ones as p90 ribosomal S6 protein kinase 2 (RSK2) inhibitors: Molecular docking simulation and structure-activity relationship analysis

Ye Zhong; Mengzhu Xue; Xue Zhao; Jun Yuan; Xiaofeng Liu; Jin Huang; Zhenjiang Zhao; Honglin Li; Yufang Xu

doi:10.1016/j.bmc.2013.01.047

Substituted indolin-2-ones as p90 ribosomal S6 protein kinase 2 (RSK2) inhibitors: Molecular docking simulation and structure-activity relationship analysis

Ye Zhong, Mengzhu Xue, Xue Zhao, Jun Yuan, Xiaofeng Liu, Jin Huang, Zhenjiang Zhao^*, Honglin Li, Yufang Xu

^*Corresponding author for this work

East China University of Science and Technology

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

A series of novel indolin-2-ones inhibitors against p90 ribosomal S6 protein kinase 2 (RSK2) were designed and synthesized and their structure-activity relationship (SAR) was studied. The most potent inhibitor, compound 3s, exhibited potent inhibition against RSK2 with an IC₅₀ value of 0.5 μM and presented a satisfactory selectivity against 23 kinases. The interactions of these inhibitors with RSK2 were investigated based on the proposed binding poses with molecular docking simulation. Four compounds and six compounds exhibited moderate anti-proliferation activities against PC 3 cells and MCF-7 cells, respectively.

Original language	English
Pages (from-to)	1724-1734
Number of pages	11
Journal	Bioorganic and Medicinal Chemistry
Volume	21
Issue number	7
DOIs	https://doi.org/10.1016/j.bmc.2013.01.047
State	Published - 1 Apr 2013
Externally published	Yes

Keywords

Kinase inhibitor
Molecular docking
RSK2

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10.1016/j.bmc.2013.01.047

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abstract = "A series of novel indolin-2-ones inhibitors against p90 ribosomal S6 protein kinase 2 (RSK2) were designed and synthesized and their structure-activity relationship (SAR) was studied. The most potent inhibitor, compound 3s, exhibited potent inhibition against RSK2 with an IC50 value of 0.5 μM and presented a satisfactory selectivity against 23 kinases. The interactions of these inhibitors with RSK2 were investigated based on the proposed binding poses with molecular docking simulation. Four compounds and six compounds exhibited moderate anti-proliferation activities against PC 3 cells and MCF-7 cells, respectively.",

keywords = "Kinase inhibitor, Molecular docking, RSK2",

author = "Ye Zhong and Mengzhu Xue and Xue Zhao and Jun Yuan and Xiaofeng Liu and Jin Huang and Zhenjiang Zhao and Honglin Li and Yufang Xu",

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T2 - Molecular docking simulation and structure-activity relationship analysis

AU - Zhong, Ye

AU - Xue, Mengzhu

AU - Zhao, Xue

AU - Yuan, Jun

AU - Liu, Xiaofeng

AU - Huang, Jin

AU - Zhao, Zhenjiang

AU - Li, Honglin

AU - Xu, Yufang

PY - 2013/4/1

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AB - A series of novel indolin-2-ones inhibitors against p90 ribosomal S6 protein kinase 2 (RSK2) were designed and synthesized and their structure-activity relationship (SAR) was studied. The most potent inhibitor, compound 3s, exhibited potent inhibition against RSK2 with an IC50 value of 0.5 μM and presented a satisfactory selectivity against 23 kinases. The interactions of these inhibitors with RSK2 were investigated based on the proposed binding poses with molecular docking simulation. Four compounds and six compounds exhibited moderate anti-proliferation activities against PC 3 cells and MCF-7 cells, respectively.

KW - Kinase inhibitor

KW - Molecular docking

KW - RSK2

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DO - 10.1016/j.bmc.2013.01.047

M3 - 文章

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AN - SCOPUS:84875221928

SN - 0968-0896

VL - 21

SP - 1724

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JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 7

ER -

Substituted indolin-2-ones as p90 ribosomal S6 protein kinase 2 (RSK2) inhibitors: Molecular docking simulation and structure-activity relationship analysis

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Keywords

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