fragment-based ligand discovery

被引：45

作者：

Fischer, Marcus ^{[1
]}

Hubbard, Roderick E. ^{[1
,2
,3
]}

机构：

[1] Univ York, York Struct Biol Lab, York YO10 5YW, N Yorkshire, England

[2] Univ York, Hull York Med Sch, York YO10 5YW, N Yorkshire, England

[3] Vernalis Ltd, Cambridge CB21 6GB, England

来源：

MOLECULAR INTERVENTIONS | 2009年 / 9卷 / 01期

基金：

英国生物技术与生命科学研究理事会;

关键词：

DRUG DISCOVERY; PROMISCUOUS INHIBITORS; KINASE INHIBITOR; BINDING-SITES; NMR; DESIGN; PROTEINS; AFFINITY; SAR; LINKING;

D O I：

10.1124/mi.9.1.7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Over the past five years, fragment-based ligand discovery has come of age. A number of compounds that evolved from fragments have entered the clinic, and the approach is increasingly accepted as an additional route to identifying new hit compounds in pharmaceutical discovery and inhibitor design. This review will summarize the current methods and ideas prevalent in the area. We will discuss the key concepts and advantages of fragment-based discovery, the approaches adopted in designing fragment libraries, the experimental methods that have been optimized for detecting fragment binding, and the strategies for evolving fragments to hit and lead compounds.

引用

页码：22 / 30

页数：9

共 45 条

[1]

Fragment-based discovery of hepatitis C virus NS5b RNA polymerase inhibitors [J].

Antonysamy, Stephen S. ;

Aubol, Brandon ;

Blaney, Jeff ;

Browner, Michelle F. ;

Giannetti, Anthony M. ;

Harris, Seth F. ;

Hebert, Normand ;

Hendle, Joerg ;

Hopkins, Stephanie ;

Jefferson, Elizabeth ;

Kissinger, Charles ;

Leveque, Vincent ;

Marciano, David ;

McGee, Ethel ;

Najera, Isabel ;

Nolan, Brian ;

Tomimoto, Masaki ;

Torres, Eduardo ;

Wright, Tobi .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (09) :2990-2995

[2]

Scaffold-based discovery of indeglitazar, a PPAR pan-active anti-diabetic agent [J].

Artis, Dean R. ;

Lin, Jack J. ;

Zhang, Chao ;

Wang, Weiru ;

Mehra, Upasana ;

Perreault, Mylene ;

Erbe, David ;

Krupka, Heike I. ;

England, Bruce P. ;

Arnold, James ;

Plotnikov, Alexander N. ;

Marimuthu, Adhirai ;

Nguyen, Hoa ;

Will, Sarah ;

Signaevsky, Maxime ;

Kral, John ;

Cantwell, John ;

Settachatgull, Calvin ;

Yan, Douglas S. ;

Fong, Daniel ;

Oh, Angela ;

Shi, Shenghua ;

Womack, Patrick ;

Powell, Benjamin ;

Habets, Gaston ;

West, Brian L. ;

Zhang, Kam Y. J. ;

Milburn, Michael V. ;

Vlasuk, George P. ;

Hirth, K. Peter ;

Nolop, Keith ;

Bollag, Gideon ;

Ibrahim, Prabha N. ;

Tobin, James F. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (01) :262-267

[3]

Barril X, 2004, MINI-REV MED CHEM, V4, P779

[4]

Drug-like annotation and duplicate analysis of a 23-supplier chemical database totalling 2.7 million compounds [J].

Baurin, N ;

Baker, R ;

Richardson, C ;

Chen, I ;

Foloppe, N ;

Potter, A ;

Jordan, A ;

Roughley, S ;

Parratt, M ;

Greaney, P ;

Morley, D ;

Hubbard, RE .

JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, 2004, 44 (02) :643-651

[5]

Bohacek RS, 1996, MED RES REV, V16, P3, DOI 10.1002/(SICI)1098-1128(199601)16:1<3::AID-MED1>3.0.CO

[6]

2-6

[7]

4,5-diarylisoxazole HSP90 chaperone inhibitors: Potential therapeutic agents for the treatment of cancer [J].

Brough, Paul A. ;

Aherne, Wynne ;

Barril, Xavier ;

Borgognoni, Jenifer ;

Boxall, Kathy ;

Cansfield, Julie E. ;

Cheung, Kwai-Miny J. ;

Collins, Ian ;

Davies, Nicholas G. M. ;

Drysdale, Martin J. ;

Dymock, Brian ;

Eccles, Suzanne A. ;

Finch, Harry ;

Fink, Alexandra ;

Hayes, Angela ;

Howes, Robert ;

Hubbard, Roderick E. ;

James, Karen ;

Jordan, Allan M. ;

Lockie, Andrea ;

Martins, Vanessa ;

Massey, Andrew ;

Matthews, Thomas P. ;

McDonald, Edward ;

Northfield, Christopher J. ;

Pearl, Laurence H. ;

Prodromou, Chrisostomos ;

Ray, Stuart ;

Raynaud, Florence I. ;

Roughley, Stephen D. ;

Sharp, Swee Y. ;

Surgenor, Allan ;

Walmsley, D. Lee ;

Webb, Paul ;

Wood, Mike ;

Workman, Paul ;

Wrightt, Lisa .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (02) :196-218

[8]

Discovery of an Aurora kinase inhibitor through site-specific dynamic combinatorial chemistry [J].

Cancilla, Mark T. ;

He, Molly M. ;

Viswanathan, Nina ;

Simmons, Robert L. ;

Taylor, Meggin ;

Fung, Amy D. ;

Cao, Kathy ;

Erlanson, Daniel A. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (14) :3978-3981

[9]

A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design [J].

Card, GL ;

Blasdel, L ;

England, BP ;

Zhang, C ;

Suzuki, Y ;

Gillette, S ;

Fong, D ;

Ibrahim, PN ;

Artis, DR ;

Bollag, G ;

Milburn, MV ;

Kim, SH ;

Schlessinger, J ;

Zhang, KYJ .

NATURE BIOTECHNOLOGY, 2005, 23 (02) :201-207

[10]

Inhibition of Mycobacterium tuberculosis Pantothenate Synthetase by Analogues of the Reaction Intermediate [J].

Ciulli, Alessio ;

Scott, Duncan E. ;

Ando, Michiyo ;

Reyes, Fernando ;

Saldanha, S. Adrian ;

Tuck, Kellie L. ;

Chirgadze, Dimitri Y. ;

Blundell, Tom L. ;

Abell, Chris .

CHEMBIOCHEM, 2008, 9 (16) :2606-2611

← 1 2 3 4 5 →