Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation | Zendy

Torkild Visnes | Zendy; Armando CázaresKörner | Zendy; Wenjing Hao | Zendy; Olov Wallner | Zendy; Geoffrey Masuyer | Zendy; Olga Loseva | Zendy; Oliver Mortusewicz | Zendy; Elisée Wiita | Zendy; Antonio Sarno | Zendy; Aleksandr Manoilov | Zendy; Juan AstorgaWells | Zendy; AnnSofie Jemth | Zendy; Lang Pan | Zendy; Kumar Sanjiv | Zendy; Stella Karsten | Zendy; Camilla Göktürk | Zendy; Maurice Grube | Zendy; Evert Homan | Zendy; Bishoy Hanna | Zendy; Cynthia B. J. Paulin | Zendy; Therese Pham | Zendy; Azita Rasti | Zendy; Ulrika Warpman Berglund | Zendy; Catharina Von Nicolai | Zendy; Carlos BenítezBuelga | Zendy; Tobias Koolmeister | Zendy; Dag Ivanic | Zendy; Petar Iliev | Zendy; Martin Scobie | Zendy; Hans E. Krokan | Zendy; Paweł Baranczewski | Zendy; Per Artursson | Zendy; Mikael Altun | Zendy; Annika Jenmalm Jensen | Zendy; Christina Kalderén | Zendy; Xueqing Ba | Zendy; Roman A. Zubarev | Zendy; Pål Stenmark | Zendy; István Boldogh | Zendy; Thomas Helleday | Zendy

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Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation

Author(s) -

Torkild Visnes,

Armando CázaresKörner,

Wenjing Hao,

Olov Wallner,

Geoffrey Masuyer,

Olga Loseva,

Oliver Mortusewicz,

Elisée Wiita,

Antonio Sarno,

Aleksandr Manoilov,

Juan AstorgaWells,

AnnSofie Jemth,

Lang Pan,

Kumar Sanjiv,

Stella Karsten,

Camilla Göktürk,

Maurice Grube,

Evert Homan,

Bishoy Hanna,

Cynthia B. J. Paulin,

Therese Pham,

Azita Rasti,

Ulrika Warpman Berglund,

Catharina Von Nicolai,

Carlos BenítezBuelga,

Tobias Koolmeister,

Dag Ivanic,

Petar Iliev,

Martin Scobie,

Hans E. Krokan,

Paweł Baranczewski,

Per Artursson,

Mikael Altun,

Annika Jenmalm Jensen,

Christina Kalderén,

Xueqing Ba,

Roman A. Zubarev,

Pål Stenmark,

István Boldogh,

Thomas Helleday

Publication year - 2018

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.aar8048

Subject(s) - proinflammatory cytokine , inflammation , dna glycosylase , dna damage , dna , dna repair , tumor necrosis factor alpha , reactive oxygen species , guanine , gene expression , biology , promoter , microbiology and biotechnology , chemistry , gene , immunology , biochemistry , nucleotide

DNA binding as an anti-inflammatory Mice that lack the gene encoding 8-oxoguanine DNA glycosylase 1 (OGG1) show resistance to inflammation. This enzyme binds to sites of oxidative DNA damage and initiates DNA base excision repair. Visneset al. developed a small-molecule drug that acts as a potent and selective active-site inhibitor that stops OGG1 from recognizing its DNA substrate (see the Perspective by Samson). The drug inhibited DNA repair and modified OGG1 chromatin dynamics, which resulted in the inhibition of proinflammatory pathway genes. The drug was well tolerated by mice and suppressed lipopolysaccharide- and tumor necrosis factor–α–mediated neutrophilic inflammation in the lungs.Science , this issue p.834 ; see also p.748

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