Small Molecule Compounds That Inhibit Antioxidant Response Gene Expression in an Inducer-Dependent Manner.
Small Molecule Compounds That Inhibit Antioxidant Response Gene Expression in an Inducer-Dependent Manner.
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DOI：
10.1021/acsinfecdis.9b00416
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发表时间：
2020-03-13
影响因子：
5.3
通讯作者：
Basler CF
中科院分区：
文献类型：
--
作者：
Edwards MR;Liu G;De S;Sourimant J;Pietzsch C;Johnson B;Amarasinghe GK;Leung DW;Bukreyev A;Plemper RK;Aron Z;Bowlin TL;Moir DT;Basler CF
Marburg virus (MARV) causes severe disease in humans and is known to activate Nrf2, the major transcription factor of the antioxidant response. Canonical activation of Nrf2 involves oxidative or electrophilic stress that prevents Keap1 targeted degradation of Nrf2, leading to Nrf2 stabilization and activation of the antioxidant response. MARV activation of Nrf2 is non-canonical, with the MARV VP24 protein (mVP24) interacting with Keap1, freeing Nrf2 from degradation. A high throughput screening (HTS) assay was developed to identify inhibitors of mVP24-induced Nrf2 activity and used to screen more than 55,000 compounds. Hit compounds were further screened against secondary HTS assays for inhibition of antioxidant activity induced by additional canonical and non-canonical mechanisms. This pipeline identified 14 compounds that suppress the response, dependent on the inducer, with 50% inhibitory concentrations below 5 μM and selectivity index values greater than 10. Notably, several of the identified compounds specifically inhibit mVP24-induced Nrf2 activity.
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影响因子：
16.6
作者：
Ladds MJGW;van Leeuwen IMM;Drummond CJ;Chu S;Healy AR;Popova G;Pastor Fernández A;Mollick T;Darekar S;Sedimbi SK;Nekulova M;Sachweh MCC;Campbell J;Higgins M;Tuck C;Popa M;Safont MM;Gelebart P;Fandalyuk Z;Thompson AM;Svensson R;Gustavsson AL;Johansson L;Färnegårdh K;Yngve U;Saleh A;Haraldsson M;D'Hollander ACA;Franco M;Zhao Y;Håkansson M;Walse B;Larsson K;Peat EM;Pelechano V;Lunec J;Vojtesek B;Carmena M;Earnshaw WC;McCarthy AR;Westwood NJ;Arsenian-Henriksson M;Lane DP;Bhatia R;McCormack E;Laín S
通讯作者：
Laín S
影响因子：
3.7
作者：
Ivanov AV;Smirnova OA;Ivanova ON;Masalova OV;Kochetkov SN;Isaguliants MG
通讯作者：
Isaguliants MG
DOI：
10.1164/rccm.200804-535oc
发表时间：
2009-01-15
影响因子：
24.7
作者：
Cho, Hye-Youn;Imani, Farhad;Kleeberger, Steven R.
通讯作者：
Kleeberger, Steven R.
影响因子：
5.4
作者：
Basu, Arnab;Antanasijevic, Aleksandar;Bowlin, Terry L.
通讯作者：
Bowlin, Terry L.
影响因子：
21.3
作者：
Komatsu, Masaaki;Kurokawa, Hirofumi;Yamamoto, Masayuki
通讯作者：
Yamamoto, Masayuki