Fueling Open-Source Drug Discovery: 177 Small-Molecule Leads against Tuberculosis

被引：267

作者：

Ballell, Lluis ^{[1
]}

Bates, Robert H. ^{[1
]}

Young, Rob J. ^{[2
]}

Alvarez-Gomez, Daniel ^{[1
]}

Alvarez-Ruiz, Emilio ^{[1
]}

Barroso, Vanessa ^{[1
]}

Blanco, Delia ^{[1
]}

Crespo, Benigno ^{[1
]}

Escribano, Jaime ^{[1
]}

Gonzalez, Ruben ^{[1
]}

Lozano, Sonia ^{[1
]}

Huss, Sophie ^{[1
]}

Santos-Villarejo, Angel ^{[1
]}

Julio Martin-Plaza, Jose ^{[1
]}

Mendoza, Alfonso ^{[1
]}

Jose Rebollo-Lopez, Maria ^{[1
]}

Remuinan-Blanco, Modesto ^{[1
]}

Luis Lavandera, Jose ^{[1
]}

Perez-Herran, Esther ^{[1
]}

Javier Gamo-Benito, Francisco ^{[1
]}

Francisco Garcia-Bustos, Jose ^{[1
]}

Barros, David ^{[1
]}

Castro, Julia P. ^{[1
]}

Cammack, Nicholas ^{[1
]}

机构：

[1] GlaxoSmithKline GSK, Madrid, Spain

[2] GlaxoSmithKline GSK, Med Res Ctr, CSC Med Chem, Stevenage SG1 2NY, Herts, England

来源：

CHEMMEDCHEM | 2013年 / 8卷 / 02期

关键词：

drug discovery; high-throughput screening; open innovation; tuberculosis; MYCOBACTERIUM-TUBERCULOSIS; CHALLENGES; INHIBITORS;

D O I：

10.1002/cmdc.201200428

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

With the aim of fuelling open-source, translational, early-stage drug discovery activities, the results of the recently completed antimycobacterial phenotypic screening campaign against Mycobacterium bovis BCG with hit confirmation in M. tuberculosis H37Rv were made publicly accessible. A set of 177 potent non-cytotoxic H37Rv hits was identified and will be made available to maximize the potential impact of the compounds toward a chemical genetics/proteomics exercise, while at the same time providing a plethora of potential starting points for new synthetic lead-generation activities. Two additional drug-discovery-relevant datasets are included: a) a drug-like property analysis reflecting the latest lead-like guidelines and b) an early lead-generation package of the most promising hits within the clusters identified.

引用

页码：313 / 321

页数：9

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