Abstract
Benzoxathiole derivatives have been used in the treatment of acne and have shown cytostatic, antipsoriatic, and antibacterial properties. However, little is known about the molecular basis for these pharmacological properties, although nuclear factor (NF)-kappaB activation is closely linked to inflammation and cell proliferation. Here, we demonstrate that the novel small-molecule benzoxathiole 6,6-dimethyl-2-(phenylimino)-6,7-dihydro-5H-benzo-[1,3]oxathiol-4-one (BOT-64) inhibits NF-kappaB activation with an IC(50) value of 1 muM by blocking inhibitory kappaB(IkappaB) kinase beta (IKKbeta), and suppresses NF-kappaB-regulated expression of inflammatory genes in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. BOT-64 inhibits IKKbeta-mediated IkappaBalpha phosphorylation in LPS-activated macrophages, resulting in sequential prevention of downstream events, including proteolytic degradation of IkappaBalpha, DNA binding ability, and transcriptional activity of NF-kappaB. BOT-64 inhibits LPS-inducible IKKbeta activity in the cells and catalytic activity of highly purified IKKbeta. Moreover, the effect of BOT-64 on cell-free IKKbeta was abolished by substitution of Ser-177 and Ser-181 residues in the activation loop of IKKbe...Continue Reading
References
Oct 28, 1988·Science·P A Baeuerle, D Baltimore
Oct 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·C J LowensteinW J Murphy
Mar 15, 1994·Proceedings of the National Academy of Sciences of the United States of America·Y ZhangW N Rom
Oct 1, 1993·Molecular and Cellular Biology·J HiscottG Bensi
Feb 1, 1993·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·S Archer
Apr 1, 1996·Molecular and Cellular Biology·J DiDonatoM Karin
Nov 1, 1996·Archives of Surgery·R D ActonD L Dunn
Jul 11, 1997·The Journal of Biological Chemistry·J YaoS T Fan
Aug 28, 1998·Science·E ZandiM Karin
Nov 17, 1998·Nature·M J YinR B Gaynor
Apr 9, 1999·Science·M DelhaseM Karin
May 27, 1999·Genes & Development·Q LiI M Verma
Jun 8, 1999·The Journal of Experimental Medicine·Z W LiM Karin
Sep 10, 1999·The Journal of Biological Chemistry·Y YamamotoR B Gaynor
Jun 3, 2000·Annual Review of Immunology·M Karin, Y Ben-Neriah
Oct 31, 2000·Gastroenterology·C K WeberR M Schmid
Mar 21, 2001·Cellular Signalling·M Guha, N Mackman
Apr 26, 2001·Analytical Biochemistry·K Y MoonY S Kim
Apr 19, 2002·Molecular Pharmacology·Maeve SheehanBasilia Zingarelli
May 29, 2002·Cardiovascular Research·Domenica AltavillaFrancesco Squadrito
Jun 11, 2002·Nature Immunology·Yoshinori NagaiKensuke Miyake
Feb 15, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·S D ChauhanA Ahluwalia
Apr 5, 2003·Blood·Stephan MathasBernd Dorken
May 20, 2003·Experimental & Molecular Medicine·Kye-Im JeonDae-Myung Jue
Jun 11, 2003·Recent Progress in Hormone Research·Bing Tian, Allan R Brasier
Jun 20, 2003·Molecular Pharmacology·Mei-Chih LiangThomas D Gilmore
Jun 26, 2003·Bioorganic & Medicinal Chemistry Letters·Alfredo C CastroJulian Adams
Sep 18, 2003·Arthritis and Rheumatism·Kim W McIntyreJames R Burke
Jul 1, 2004·Bioorganic & Medicinal Chemistry Letters·Toshiki MurataTimothy B Lowinger
Dec 2, 2005·The Journal of Biological Chemistry·Michel BernierSutapa Kole
Mar 15, 2006·American Journal of Physiology. Lung Cellular and Molecular Physiology·Shu Fang Liu, Asrar B Malik
Sep 16, 2006·Biochemical Pharmacology·Sabine OlivierVincent Bours
Jan 18, 2007·Expert Opinion on Therapeutic Targets·Brendan O'SullivanRanjeny Thomas
Aug 3, 2007·Biochemical and Biophysical Research Communications·Byung Hak KimYoungsoo Kim
Citations
Apr 6, 2011·Inflammation·Ji-Won ParkKyung-Seop Ahn
Jul 31, 2013·Inflammation·Guan-Wei FanXiumei Gao
May 7, 2011·Archives of Pharmacal Research·Dong-Soon Im
Jul 1, 1994·Trends in Pharmacological Sciences·S Ruetz, P Gros
Mar 16, 2011·The Journal of Infectious Diseases·Eunmiri RohYoungsoo Kim
Sep 2, 2011·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Jun YingXi-Sha Wang
Oct 5, 2010·PloS One·Wei-Bing SongZhen-Shu Zhang
Apr 19, 2011·Experimental & Molecular Medicine·Byung Hak KimSang Kyu Ye
Jan 16, 2014·Inflammation·Zheng-Gang LuanXiao-Chun Ma
Aug 28, 2014·Biochemical Pharmacology·Karen HeyninckWim Vanden Berghe
Oct 1, 2013·Mediators of Inflammation·Bing-rong ZhouDan Luo
Dec 18, 2009·Mediators of Inflammation·Zhang XipingMa Meili
Jun 15, 2011·Food Chemistry·Umeo TakahamaRyo Yamauchi
Sep 20, 2011·Free Radical Biology & Medicine·Younghwa KimTae-Yoon Kim
Jul 31, 2013·Cancer Cell·Ariel PribludaYinon Ben-Neriah
Aug 1, 2015·Scientific Reports·He JunLuo Junqiu
Jul 6, 2017·Antioxidants·Umeo Takahama, Sachiko Hirota
Feb 20, 2010·Free Radical Research·Umeo TakahamaSachiko Hirota
Nov 20, 2009·British Journal of Pharmacology·E-Y ChungY Kim
May 11, 2018·Molecular Pharmacology·Zhibo GaiGerd A Kullak-Ublick
Aug 4, 2020·Journal of Leukocyte Biology·Chloe M McKee, Rebecca C Coll
Apr 12, 2012·British Journal of Pharmacology·Hwa Young LeeYoungsoo Kim
Aug 26, 2018·Cells·Jack A Prescott, Simon J Cook
Jan 1, 2012·Biomolecules & Therapeutics·Woong-Hyun KimHyun Park
Aug 13, 2008·The Journal of Pharmacology and Experimental Therapeutics·Byung Hak KimYoungsoo Kim
Sep 18, 2015·Oncotarget·Ting LiLiang Liu
Sep 20, 2019·The Korean Journal of Parasitology·Maryam Hakimi PariziSaeid Hassanzadeh
Dec 22, 2020·European Journal of Immunology·Goutham VansarlaCaroline Bergenfelz
Feb 10, 2021·European Journal of Pharmacology·Tácio N SouzaEmiliano Barreto
Sep 29, 2018·Molecular Pharmaceutics·Mingzheng PengJinwu Wang