Structure-Based Discovery of Natural-Product-like TNF-α Inhibitors

被引：106

作者：

Chan, Daniel Shiu-Hin ^{[1
,2
]}

Lee, Ho-Man ^{[1
,2
]}

Yang, Fang ^{[1
,2
]}

Che, Chi-Ming ^{[1
,2
]}

Wong, Catherine C. L. ^{[3
]}

Abagyan, Ruben ^{[4
]}

Leung, Chung-Hang ^{[1
,2
]}

Ma, Dik-Lung ^{[5
]}

机构：

[1] Univ Hong Kong, Dept Chem, Inst Mol Technol Drug Discovery & Synth, Hong Kong, Hong Kong, Peoples R China

[2] Univ Hong Kong, Open Lab Chem Biol, Inst Mol Technol Drug Discovery & Synth, Hong Kong, Hong Kong, Peoples R China

[3] Scripps Res Inst, Dept Physiol Chem, La Jolla, CA 92037 USA

[4] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA USA

[5] Hong Kong Baptist Univ, Dept Chem, Kowloon Tong, Hong Kong, Peoples R China

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2010年 / 49卷 / 16期

关键词：

drug discovery; inhibitors; natural products; tumor necrosis factor; virtual screening; ACTIVATION; THERAPIES; BINDING; KINASE;

D O I：

10.1002/anie.200907360

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

(Figure Presented) Small but effective: Two natural-productlike inhibitors of tumor necrosis factor α (TNF-α represented in green in the picture) have been identified using structure-based virtual screening. These compounds represent only the third and fourth examples of direct targeting of TNF-α by a small molecule. and display potency comparable to that of the strongest TNF-α inhibitor reported to date. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.

引用

页码：2860 / 2864

页数：5

共 23 条

[1] Signalling pathways of the TNF superfamily: A double-edged sword [J].

Aggarwal, BB .

NATURE REVIEWS IMMUNOLOGY, 2003, 3 (09) :745-756

[2]

ALZANI R, 1993, J BIOL CHEM, V268, P12526

[3]

Breinbauer R, 2002, ANGEW CHEM INT EDIT, V41, P2879

[4]

BREINBAUER R, 2002, ANGEW CHEM, V114, P3002

[5] BMS-345541 is a highly selective inhibitor of IκB kinase that binds at an allosteric site of the enzyme and blocks NF-κB-dependent transcription in mice [J].

Burke, JR ;

Pattoli, MA ;

Gregor, KR ;

Brassil, PJ ;

MacMaster, JF ;

McIntyre, KW ;

Yang, XX ;

Iotzova, VS ;

Clarke, W ;

Strnad, J ;

Qiu, YP ;

Zusi, FC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (03) :1450-1456

[6] Anti-TNF-α antibody therapies in autoimmune diseases [J].

Chatzantoni, Kokona ;

Mouzaki, Athanasia .

CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2006, 6 (16) :1707-1714

[7] Identification of inhibitors for mycobacterial protein tyrosine phosphatase B (MptpB) by biology-oriented synthesis (BIOS) [J].

Correa, Ivan R., Jr. ;

Noeren-Mueller, Andrea ;

Ambrosi, Horst-Dieter ;

Jakupovic, Sven ;

Saxena, Krishna ;

Schwalbe, Harald ;

Kaiser, Markus ;

Waldmann, Herbert .

CHEMISTRY-AN ASIAN JOURNAL, 2007, 2 (09) :1109-1126

[8] Natural product-likeness score and its application for prioritization of compound libraries [J].

Ertl, Peter ;

Roggo, Silvio ;

Schuffenhauer, Ansgar .

JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2008, 48 (01) :68-74

[9] LMP-420, a small-molecule inhibitor of TNF-alpha, reduces replication of HIV-1 and Mycobacterium tuberculosis in human cells [J].

Haraguchi S. ;

Day N.K. ;

Kamchaisatian W. ;

Beigier-Pompadre M. ;

Stenger S. ;

Tangsinmankong N. ;

Sleasman J.W. ;

Pizzo S.V. ;

Cianciolo G.J. .

AIDS Research and Therapy, 3 (1)

[10] Small-molecule inhibition of TNF-α [J].

He, MM ;

Smith, AS ;

Oslob, JD ;

Flanagan, WM ;

Braisted, AC ;

Whitty, A ;

Cancilla, MT ;

Wang, J ;

Lugovskoy, AA ;

Yoburn, JC ;

Fung, AD ;

Farrington, G ;

Eldredge, JK ;

Day, ES ;

Cruz, LA ;

Cachero, TG ;

Miller, SK ;

Friedman, JE ;

Choong, IC ;

Cunningham, BC .

SCIENCE, 2005, 310 (5750) :1022-1025

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