Structure-based virtual screening approach to the discovery of p38 MAP kinase inhibitors

Hwanho Choi; Ho Jeong Park; Jong Chul Shin; Hyun Sun Ko; Jung Kyun Lee; Soyoung Lee; Hwangseo Park; Sungwoo Hong

doi:10.1016/j.bmcl.2012.01.104

Structure-based virtual screening approach to the discovery of p38 MAP kinase inhibitors

Hwanho Choi
, Ho Jeong Park
, Jong Chul Shin
, Hyun Sun Ko
, Jung Kyun Lee
, Soyoung Lee
, Hwangseo Park
, Sungwoo Hong

Department of Obstetrics and Gynecology

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

11 Scopus citations

Abstract

p38 Mitogen-activated protein kinase (MAPK) has been considered to be a promising target for the development of therapeutics for various immunologic diseases. Herein we report an example for a successful application of the virtual screening with protein-ligand docking to identify the novel inhibitors of p38α MAPK. These inhibitors were screened for having desirable physicochemical properties as a drug candidate and compound 1-3 revealed a moderate inhibitory activity with IC ₅₀ values ranging from 0.7 to 20 μM. Therefore, they deserve a consideration for further development by structure-activity relationship (SAR) studies to optimize the inhibitory activities. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of p38 MAPK are addressed in detail.

Original language	English
Pages (from-to)	2195-2199
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	6
DOIs	https://doi.org/10.1016/j.bmcl.2012.01.104
State	Published - 15 Mar 2012

Bibliographical note

Funding Information:
This research was supported by National Research Foundation of Korea (NRF) through general research grants ( NRF-2011-0003609 , 2011-0016436 ) and 2011-0020322 .

Keywords

Anti-inflammatory agents
Docking
Inhibitor
Virtual screening
p38 MAPK

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title = "Structure-based virtual screening approach to the discovery of p38 MAP kinase inhibitors",

abstract = "p38 Mitogen-activated protein kinase (MAPK) has been considered to be a promising target for the development of therapeutics for various immunologic diseases. Herein we report an example for a successful application of the virtual screening with protein-ligand docking to identify the novel inhibitors of p38α MAPK. These inhibitors were screened for having desirable physicochemical properties as a drug candidate and compound 1-3 revealed a moderate inhibitory activity with IC 50 values ranging from 0.7 to 20 μM. Therefore, they deserve a consideration for further development by structure-activity relationship (SAR) studies to optimize the inhibitory activities. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of p38 MAPK are addressed in detail.",

keywords = "Anti-inflammatory agents, Docking, Inhibitor, Virtual screening, p38 MAPK",

author = "Hwanho Choi and Park, \{Ho Jeong\} and Shin, \{Jong Chul\} and Ko, \{Hyun Sun\} and Lee, \{Jung Kyun\} and Soyoung Lee and Hwangseo Park and Sungwoo Hong",

note = "Funding Information: This research was supported by National Research Foundation of Korea (NRF) through general research grants ( NRF-2011-0003609 , 2011-0016436 ) and 2011-0020322 .",

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language = "English",

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AU - Park, Ho Jeong

AU - Shin, Jong Chul

AU - Ko, Hyun Sun

AU - Lee, Jung Kyun

AU - Lee, Soyoung

AU - Park, Hwangseo

AU - Hong, Sungwoo

N1 - Funding Information: This research was supported by National Research Foundation of Korea (NRF) through general research grants ( NRF-2011-0003609 , 2011-0016436 ) and 2011-0020322 .

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N2 - p38 Mitogen-activated protein kinase (MAPK) has been considered to be a promising target for the development of therapeutics for various immunologic diseases. Herein we report an example for a successful application of the virtual screening with protein-ligand docking to identify the novel inhibitors of p38α MAPK. These inhibitors were screened for having desirable physicochemical properties as a drug candidate and compound 1-3 revealed a moderate inhibitory activity with IC 50 values ranging from 0.7 to 20 μM. Therefore, they deserve a consideration for further development by structure-activity relationship (SAR) studies to optimize the inhibitory activities. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of p38 MAPK are addressed in detail.

AB - p38 Mitogen-activated protein kinase (MAPK) has been considered to be a promising target for the development of therapeutics for various immunologic diseases. Herein we report an example for a successful application of the virtual screening with protein-ligand docking to identify the novel inhibitors of p38α MAPK. These inhibitors were screened for having desirable physicochemical properties as a drug candidate and compound 1-3 revealed a moderate inhibitory activity with IC 50 values ranging from 0.7 to 20 μM. Therefore, they deserve a consideration for further development by structure-activity relationship (SAR) studies to optimize the inhibitory activities. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of p38 MAPK are addressed in detail.

KW - Anti-inflammatory agents

KW - Docking

KW - Inhibitor

KW - Virtual screening

KW - p38 MAPK

UR - https://www.scopus.com/pages/publications/84862798885

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DO - 10.1016/j.bmcl.2012.01.104

M3 - Article

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AN - SCOPUS:84862798885

SN - 0960-894X

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 6

ER -

Structure-based virtual screening approach to the discovery of p38 MAP kinase inhibitors

Abstract

Bibliographical note

Keywords

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