Bis-Michael Acceptors as Novel Probes to Study the Keap1/Nrf2/ARE Pathway

被引：18

作者：

Deny, Ludovic J. ^{[1
,2
]}

Traboulsi, Hussein ^{[2
,3
,4
]}

Cantin, Andre M. ^{[2
,3
,4
]}

Marsault, Eric ^{[2
,5
]}

Richter, Martin V. ^{[2
,3
,4
]}

Belanger, Guillaume ^{[1
,2
]}

机构：

[1] Univ Sherbrooke, Dept Chim, 2500 Blvd Univ, Sherbrooke, PQ J1K 2R1, Canada

[2] Univ Sherbrooke, Inst Pharmacol Sherbrooke, Sherbrooke, PQ J1H 5N4, Canada

[3] CHU Sherbrooke, Dept Med, Serv Pneumol, Sherbrooke, PQ J1H 5N4, Canada

[4] CHU Sherbrooke, Ctr Rech Clin, Sherbrooke, PQ J1H 5N4, Canada

[5] Univ Sherbrooke, Dept Pharmacol, Sherbrooke, PQ J1K 2R1, Canada

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 59卷 / 20期

关键词：

DIELS-ALDER; KEAP1-NRF2; PATHWAY; SULFHYDRYL-GROUPS; OXIDATIVE STRESS; INHIBITORS; ACTIVATORS; POTENCY; ENZYMES; BINDING; NRF2;

D O I：

10.1021/acs.jmedchem.6b01132

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator that promotes the transcription of cytoprotective genes in response to oxidative/electrophilic stress. Various Michael-type compounds were designed and synthesized, and their potency to activate the Keap1/Nrf2/ARE pathway was evaluated. Compounds bearing two Michael-type acceptors proved to be the most active. Tether length and rigidity between the acceptors was crucial. This study will help to understand how this feature disrupts the interaction between Keap1 and Nrf2.

引用

页码：9431 / 9442

页数：12

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