Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation-Reference-Cited by-同舟云学术

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

Published:2018-11-16 Issue:6416 Volume:362 Page:834-839
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Visnes Torkild¹²^ORCID,Cázares-Körner Armando¹^ORCID,Hao Wenjing³^ORCID,Wallner Olov¹^ORCID,Masuyer Geoffrey⁴^ORCID,Loseva Olga¹,Mortusewicz Oliver¹,Wiita Elisée¹,Sarno Antonio⁵⁶^ORCID,Manoilov Aleksandr⁷⁸,Astorga-Wells Juan⁷⁸^ORCID,Jemth Ann-Sofie¹,Pan Lang³,Sanjiv Kumar¹,Karsten Stella¹^ORCID,Gokturk Camilla¹,Grube Maurice¹,Homan Evert J.¹,Hanna Bishoy M. F.¹^ORCID,Paulin Cynthia B. J.¹^ORCID,Pham Therese¹,Rasti Azita¹,Berglund Ulrika Warpman¹,von Nicolai Catharina¹,Benitez-Buelga Carlos¹,Koolmeister Tobias¹,Ivanic Dag¹^ORCID,Iliev Petar¹^ORCID,Scobie Martin¹^ORCID,Krokan Hans E.⁵⁶,Baranczewski Pawel⁷⁹¹⁰,Artursson Per⁹¹⁰^ORCID,Altun Mikael¹,Jensen Annika Jenmalm¹¹,Kalderén Christina¹,Ba Xueqing³^ORCID,Zubarev Roman A.⁷⁸¹²^ORCID,Stenmark Pål⁴¹³^ORCID,Boldogh Istvan³,Helleday Thomas¹¹⁴^ORCID

Affiliation:

1. Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, S-171 76 Stockholm, Sweden.

2. Department of Biotechnology and Nanomedicine, SINTEF Industry, N-7465 Trondheim, Norway.

3. Department of Microbiology and Immunology, Sealy Center for Molecular Medicine, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA.

4. Department of Biochemistry and Biophysics, Stockholm University, S-106 91 Stockholm, Sweden.

5. Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.

6. The Liaison Committee for Education, Research, and Innovation in Central Norway, Trondheim, Norway.

7. Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden.

8. SciLifeLab, SE-17121 Solna, Sweden.

9. Science for Life Laboratory Drug Discovery and Development Platform, ADME of Therapeutics Facility, Department of Pharmacy, Uppsala University, Uppsala, Sweden.

10. Uppsala Drug Optimisation and Pharmaceutical Profiling Platform (UDOPP), Department of Pharmacy, Uppsala University, Uppsala, Sweden.

11. Chemical Biology Consortium Sweden, Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 21 Stockholm, Sweden.

12. Department of Pharmacological and Technological Chemistry, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.

13. Department of Experimental Medical Science, Lund University, Lund, Sweden.

14. Sheffield Cancer Centre, Department of Oncology and Metabolism, University of Sheffield, Sheffield S10 2RX, UK.

Abstract

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. Visnes et 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

Funder

National Institute of Allergy and Infectious Diseases

Ragnar Soderbergs stiftelse

Torsten Soderbergs Stiftelse

Swedish Foundation for Strategic Research

Cancerfonden

Knut och Alice Wallenbergs Stiftelse

Vetenskapsrådet

Barncancerfonden

VINNOVA

Central Norway Regional Health Authority

svanhild and arne must's fund for medical resarch