Identification and SAR of squarate inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2)

被引：20

作者：

Lovering, Frank ^{[1
]}

Kirincich, Steve ^{[1
]}

Wang, Weiheng ^{[1
]}

Combs, Kerry ^{[1
]}

Resnick, Lynn ^{[3
]}

Sabalski, Joan E. ^{[3
]}

Butera, John ^{[3
]}

Liu, Julie ^{[2
]}

Parris, Kevin ^{[1
]}

Telliez, J. B. ^{[2
]}

机构：

[1] Wyeth Res, Chem Sci, Cambridge, MA 02140 USA

[2] Wyeth Res, Inflammat, Cambridge, MA 02140 USA

[3] Wyeth Res, Chem Sci, Princeton, NJ 08543 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 09期

关键词：

MAPKAP-K2; MK2; TNF; Squarate; TUMOR-NECROSIS-FACTOR; URGE URINARY-INCONTINENCE; CATALYST; DESIGN; POTENT; AMIDATION; STABILITY; RESISTANT; DISCOVERY; THERAPY;

D O I：

10.1016/j.bmc.2009.03.041

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A novel series of inhibitors for mitogen activated protein kinase-activated protein kinase 2 (MK-2) are reported. These squarate based inhibitors were identified via a high-throughput screen. An MK2 co-structure with the starting ligand was obtained and a structure based approach was followed to optimize potency and selectivity. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：3342 / 3351

页数：10

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