Chemical probes for biological systems

被引：14

作者：

Garcia-Serna, Ricard

Mestres, Jordi ^{[1
]}

机构：

[1] Inst Municipal Invest Med, Res Program Biomed Informat GRIB, Chemogenom Lab, Barcelona 08003, Catalonia, Spain

来源：

DRUG DISCOVERY TODAY | 2011年 / 16卷 / 3-4期

关键词：

DRUG DISCOVERY; MAGIC BULLETS; PHARMACOLOGY; RECEPTORS; DATABASE; LIGANDS; DESIGN;

D O I：

10.1016/j.drudis.2010.11.004

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

According to the latest definition in use by the NIH Molecular Libraries Screening Centers Network, a compound to be nominated as a chemical probe should have, on the one hand, an affinity below 100 nM for the primary target and, on the other hand, at least tenfold selectivity against related targets. Taking drugs as the ultimate product of an affinity and selectivity optimization process, it is found that only 14.4% of them would actually qualify as chemical probes under those criteria. Therefore, if chemical probes are expected to give rise to new medicines, strict adherence to the current probe definition might result in many compounds of potential therapeutic interest being overlooked.

引用

页码：99 / 106

页数：8

共 25 条

[1] In silico directed chemical probing of the adenosine receptor family [J].

Areias, Filipe M. ;

Brea, Jose ;

Gregori-Puigjane, Elisabet ;

Zaki, Magdi E. A. ;

Carvalho, M. Alice ;

Dominguez, Eduardo ;

Gutierrez-de-Teran, Hugo ;

Proenca, M. Fernanda ;

Loza, Maria I. ;

Mestres, Jordi .

BIOORGANIC & MEDICINAL CHEMISTRY, 2010, 18 (09) :3043-3052

[2] NIH Molecular Libraries Initiative [J].

Austin, CP ;

Brady, LS ;

Insel, TR ;

Collins, FS .

SCIENCE, 2004, 306 (5699) :1138-1139

[3] Computational analysis of ligand relationships within target families [J].

Bajorath, Juergen .

CURRENT OPINION IN CHEMICAL BIOLOGY, 2008, 12 (03) :352-358

[4] Multi-target-directed ligands to combat neurodegenerative diseases [J].

Cavalli, Andrea ;

Bolognesi, Maria Laura ;

Minarini, Anna ;

Rosini, Michela ;

Tumiatti, Vincenzo ;

Recanatini, Maurizio ;

Melchiorre, Carlo .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (03) :347-372

[5] In silico pharmacology for drug discovery:: methods for virtual ligand screening and profiling [J].

Ekins, S. ;

Mestres, J. ;

Testa, B. .

BRITISH JOURNAL OF PHARMACOLOGY, 2007, 152 (01) :9-20

[6] The art of the chemical probe [J].

Frye, Stephen V. .

NATURE CHEMICAL BIOLOGY, 2010, 6 (03) :159-161

[7] IUPHAR-DB: the IUPHAR database of G protein-coupled receptors and ion channels [J].

Harmar, Anthony J. ;

Hills, Rebecca A. ;

Rosser, Edward M. ;

Jones, Martin ;

Buneman, O. Peter ;

Dunbar, Donald R. ;

Greenhill, Stuart D. ;

Hale, Valerie A. ;

Sharman, Joanna L. ;

Bonner, Tom I. ;

Catterall, William A. ;

Davenport, Anthony P. ;

Delagrange, Philippe ;

Dollery, Colin T. ;

Foord, Steven M. ;

Gutman, George A. ;

Laudet, Vincent ;

Neubig, Richard R. ;

Ohlstein, Eliot H. ;

Olsen, Richard W. ;

Peters, John ;

Pin, Jean-Philippe ;

Ruffolo, Robert R. ;

Searls, David B. ;

Wright, Mathew W. ;

Spedding, Michael .

NUCLEIC ACIDS RESEARCH, 2009, 37 :D680-D685

[8] French/European academic compound library initiative [J].

Hibert, Marcel F. .

DRUG DISCOVERY TODAY, 2009, 14 (15-16) :723-725

[9]

Hill SJ, 1997, PHARMACOL REV, V49, P253

[10] Can we rationally design promiscuous drugs? [J].

Hopkins, AL ;

Mason, JS ;

Overington, JP .

CURRENT OPINION IN STRUCTURAL BIOLOGY, 2006, 16 (01) :127-136

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