Synthetic EthR inhibitors boost antituberculous activity of ethionamide

被引：0

作者：

Nicolas Willand

Bertrand Dirié

Xavier Carette

Pablo Bifani

Amit Singhal

Matthieu Desroses

Florence Leroux

Eve Willery

Vanessa Mathys

Rebecca Déprez-Poulain

Guy Delcroix

Frédéric Frénois

Marc Aumercier

Camille Locht

Vincent Villeret

Benoit Déprez

Alain R Baulard

机构：

[1] Institut National de la Santé et de la Recherche Médicale (INSERM),

[2] U761,undefined

[3] Faculté de Pharmacie de Lille,undefined

[4] Univ Lille Nord de France,undefined

[5] Institut Pasteur de Lille,undefined

[6] Institut Fédératif de Recherche 142,undefined

[7] Molecular and Cellular Medicine,undefined

[8] Pôle de Recherche Interdisciplinaire pour le Médicament,undefined

[9] INSERM U629,undefined

[10] Institut Pasteur,undefined

[11] Unité Mixte de Recherche 8161,undefined

[12] Institut de Biologie de Lille,undefined

[13] Centre National de la Recherche Scientifique (CNRS)–Univ Lille Nord de France,undefined

[14] Institut Pasteur de Lille,undefined

来源：

Nature Medicine | 2009年 / 15卷

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摘要：

Several tuberculosis drugs are prodrugs that have to be enzymatically activated during metabolism. Ethionamide is such a drug and is activated by the monooxygenase EthA. EthA is itself regulated by the transcriptional repressor EthR. Here Alain Baulard and his colleagues have designed inhibitors of EthR that boost the antimycobacterial efficacy of ethionamide both in vitro and in vivo. Current therapy with ethionamide requires the use of high doses, often eliciting side effects. Its combination with the EthR repressor should allow lower doses to be used.

引用

页码：537 / 544

页数：7

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