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Table S1 Upstream NF-B inhibitors Molecule Calagualine (fern derivative) Conophylline (Ervatamia microphylla) Evodiamine (Evodiae fructus component) Geldanamycin Type of molecule Natural product Point of inhibition Upstream of IKK (TRAF2-NIK) Natural product Down regulated TNF-Receptors Natural product AKT-IKK interaction Natural product IKK complex formation Perrilyl alcohol Natural product Calcium pathway Protein-bound polysaccharide from basidiomycetes Rocaglamides (Aglaia derivatives) 15-deoxy-prostaglandin J(2) Natural product LPS-CD14 interaction Natural product Upstream of IKK Natural product PPAR activation of NF-B Adenovirus E1A NS5A (Hepatitis C virus) NS3/4A (HCV protease) Protein, viral Protein, viral Protein Adaptor TRAF2 inhibition Upstream of IKK Golli BG21 (product of myelin basic protein) NPM-ALK oncoprotein MAST205 Protein Upstream of IKK (PKC) Protein Protein Traf2 inhibition TRAF6 binding Erbin overexpression Protein NOD2 inhibitor Rituximab (anti-CD20 antibody) Kinase suppressor of ras (KSR2) PEDF (pigment epithelium derived factor) TNAP Betaine Desloratadine LY29 and LY30 Protein Up-regulates Raf-1 kinase inhibitor Protein MEKK3 inhibitor Protein ROS generation Protein Synthetic Synthetic Synthetic NIK NIK/IKK Histamine H1 receptor PI3 Kinase inhibitors MOL 294 (small molecule) Synthetic Redox regulated activation of NF-B Pefabloc (serine protease inhibitor) Rhein Synthetic Upstream of IKK Synthetic MEKK activation of NF-B Salmeterol, fluticasone propionate Synthetic 2 agonists References Manna et al., 2003 Gohda et al., 2003 Takada et al., 2005a Chen et al., 2002b Berchtold et al., 2005 Asai et al., 2005 Baumann et al., 2002 Boyault et al., 2004 Cook et al., 2002 Park et al., 2002 Karayiannis et al., 2005 Feng et al., 2004 Horie et al., 2004 Xiong et al., 2004 McDonald et al., 2005 Jazirehi et al., 2005 Channavajhala et al., 2005 Yamagishi et al., 2004 Hu et al., 2004 Go et al., 2005 Wu et al., 2004b Choi et al., 2004a Henderson et al., 2002 Tando et al., 2002 Martin et al., 2003 Baouz et al., 2005 1 Table S2 IKK activity and IB phosphorylation inhibitors Molecule Type of molecule Point of inhibition References Lead Anandamide Artemisia vestita Cobrotoxin Inorganic Complex Natural product Natural product Natural product Xu et al., 2006 Sancho et al., 2003 Sun et al., 2006 Park et al., 2005 Dehydroascorbic acid (Vitamin C) Herbimycin A Natural product Natural product IKK activity IKK activity Phosphorylation IKK activity and p50 DNA binding IKK activity IKK activity Isorhapontigenin Manumycin A Natural product Natural product IKK activity IKK activity Pomegranate fruit extract Tetrandine (plant alkaloid) Nitric oxide Natural product Natural product Natural product IKK activity IKK activity IKK activity /IB phosphorylation Thienopyridine Acetyl-boswellic acids Natural product Natural product IKK activity IKK activity -carboline Natural product Natural product IKK activity IKK activity Natural product IKK activity Cardamomin Diosgenin Natural product Natural product IKK activity IKK activity Furonaphthoquinone Guggulsterone Natural product Natural product IKK activity IKK activity Falcarindol Honokiol Hypoestoxide Garcinone B Kahweol Kava (Piper methysticum) derivatives -mangostin (from Garcinia mangostana) N-acetylcysteine Nitrosylcobalamin (vitamin B12 analog) Natural product Natural product Natural product Natural product Natural product Natural product Natural product Natural product Natural product IKK activity IKK activity IKK activity IKK activity IKK activity IKK activity IKK activity IKK activity IKK activity Piceatannol Plumbagin (5-hydroxy-2-methyl-1,4naphthoquinone) Quercetin Rosmarinic acid Semecarpus anacardiu extract Staurosporine Natural product Natural product IKK activity IKK activity Carcamo et al., 2004 Iwasaki et al., 1992; Mahon & O’Neill, 1995; Ogino et al., 2004 Li et al., 2005 Bernier et al., 2005; Frassanito et al., 2005 Afaq et al., 2004 Ho et al., 2004 Katsuyama et al., 1998; Matthews et al., 1996; Spieker & Liao, 1999; Reynaert et al., 2004 Morwick et al., 2006 Syrovets et al., 2004, 2005 Yoon et al., 2005 Ichikawa et al., 2005; Ito et al., 2005 Shukla & Gupta, 2004; Yoon et al., 2006 Lee et al., 2005 Shishodia & Aggarwal, 2005; Liagre et al., 2005 Shin et al., 2006 Ichikawa & Aggarwal, 2006 Shiao et al., 2005 Tse et al., 2005 Ojo-Amaize et al., 2001 Yamakuni et al., 2005 Kim et al., 2004 Folmer et al., 2006 Nakatani et al., 2004 Oka et al., 2000 Chawla-Sarkar et al., 2003 Islam et al., 2004 Sandur et al., 2006 Natural product Natural product Natural product Natural product IKK activity IKK activity IKK activity IKK activity Peet & Li, 1999 Lee et al., 2006c Singh et al., 2006 Peet & Li, 1999 1'-Acetoxychavicol acetate (Languas galanga) Apigenin (plant flavinoid) 2 Sulforaphane and phenylisothiocyanate Theaflavin (black tea component) Tilianin -Tocotrienol Wedelolactone Withanolides Zerumbone Silibinin Natural product Natural product Natural product Natural product Natural product Natural product Natural product Natural product Betulinic acid Natural product Ursolic acid Natural product Monochloramine and glycine chloramine (NH2Cl) Anethole Baoganning Black raspberry extracts (cyanidin 3-Oglucoside, cyanidin 3-O-(2(G)xylosylrutinoside), cyanidin 3-Orutinoside) Buddlejasaponin IV Cacospongionolide B Calagualine Carbon monoxide Cardamonin Cycloepoxydon; 1-hydroxy-2hydroxymethyl-3-pent-1-enylbenzene Decursin Dexanabinol Digitoxin Diterpenes Docosahexaenoic acid Extensively oxidized low density lipoprotein (ox-LDL), 4-Hydroxynonenal (HNE) Flavopiridol Natural product IKK activity Activation of IKK Activation of IKK IKK activity IKK activity Activation of IKK Activation of IKK IKK activity; nuclear translocation IKK activity and p65 phosphorylation IKK activity and p65 phosphorylation Oxidizes IB Xu et al., 2005 Aneja et al., 2004 Nam et al., 2005 Shah & Sylvester, 2005 Kobori et al., 2003 Ichikawa et al., 2006 Takada et al., 2005 Dhanalakshmi et al., 2002; Singh et al., 2004 Takada & Aggarwal, 2003 Shishodia et al., 2003 Natural product Natural product Natural product Phosphorylation Phosphorylation Phosphorylation Natural product Natural product Natural product Natural product Natural product Natural product Phosphorylation Phosphorylation Phosphorylation Phosphorylation Phosphorylation Phosphorylation Won et al., 2006 Posadas et al, 2003 Manna et al, 2003 Sarady et al, 2002 Israf et al, 2006 Gehrt et al., 1998 Natural product Natural product Natural product Natural product Natural product Natural product Phosphorylation Phosphorylation Phosphorylation Phosphorylation Phosphorylation Phosphorylation Kim et al., 2006 Juttler et al., 2004 Srivastava et al., 2004 Chao et al., 2005 Chen et al., 2005b Brand et al., 1997; Page et al., 1999 Natural product [6]-gingerol; casparol Natural product IKK activity and RelA phosphorylation Phosphorylation Glossogyne tenuifolia Natural product Phosphorylation Guggulsterone Natural product Phosphorylation Indirubin-3'-oxime Licorce extracts Oleandrin Natural product Natural product Natural product Phosphorylation Phosphorylation Phosphorylation Omega 3 fatty acids Panduratin A (from Kaempferia pandurata, Zingiberaceae) Petrosaspongiolide M Pinosylvin Plagius flosculosus extract polyacetylene Natural product Natural product Phosphorylation Phosphorylation Takada & Aggarwal, 2003 Kim et al., 2005j; Aktan et al., 2006 Wu et al., 2004a; Ha et al., 2006 Shishodia & Aggarwal, 2004 Mak et al., 2004 Kim et al., 2006e Manna et al., 2000f; Sreeivasan et al., 2003 Novak et al., 2002 Yun et al., 2003 Natural product Natural product Natural product Phosphorylation Phosphorylation Phosphorylation Posadas et al., 2003b Lee et al., 2006c Calzado et al., 2005 Kim et al., 2005; Midwinter et al., 2006 Chainy et al., 2000 Tan et al., 2005 Huang et al., 2002; Hecht et al., 2006 3 spiroketal Phytic acid (inositol hexakisphosphate) Pomegranate fruit extract Prostaglandin A1 20(S)-Protopanaxatriol (ginsenoside metabolite) Rengyolone Rottlerin Saikosaponin-d Saline (low Na+ istonic) Salvia miltiorrhizae water-soluble extract Sanguinarine (pseudochelerythrine, 13methyl-[1,3]-benzodioxolo-[5,6-c]-1,3dioxolo-4,5 phenanthridinium) Sesquiterpene lactones (parthenolide; ergolide; guaianolides) Natural product Natural product Natural product Natural product Phosphorylation Phosphorylation Phosphorylation/IKK Phosphorylation Natural product Natural product Natural product Natural product Natural product Natural product Phosphorylation Phosphorylation Phosphorylation Phosphorylation Phosphorylation Phosphorylation Natural product IKK and DNA binding Scoparone Silymarin Natural product Natural product Phosphorylation Phosphorylation Sulindac Vesnarinone Natural product Natural product IKK/Phosphorylation Phosphorylation Xanthoangelol D IKK peptide to NEMO binding domain NEMO CC2-LZ peptide Adenovirus E3-14.7K Adenovirus E3-10.4/14.5K Natural product Peptide Peptide Protein, viral Protein, viral Phosphorylation IKK-NEMO interaction NEMO oligomerization IKK activity IKK activity Core protein (Hepatitis C virus) E7 (Papillomavirus) MC160 (Mollusum Contagiosum virus) Protein, viral Protein, viral Protein, viral IKK activity IKK activity IKK activity MC159 (Mollusum contagiosum virus) NS5B (Hepatitis C virus) vIRF3 (KSHV) Cytomegalovirus HB-EGF (Heparin-binding epidermal growth factor-like growth factor) Hepatocyte growth factor PAN1 (aka NALP2 or PYPAF2) PTEN (tumor suppressor) Interleukin-10 Protein, viral Protein, viral Protein, viral Protein, viral Protein Reduced IKK expression IKK activity IKK activity Phosphorylation IKK activity Protein Protein Protein Protein Anti-thrombin III Chorionic gonadotropin FHIT (Fragile histidine triad protein) Protein Protein Protein IKK activity IKK activity Activation of IKK Reduced IKK and IKK expression Phosphorylation Phosphorylation Phosphorylation Interferon- SOCS1 Protein Protein Phosphorylation Phosphorylation AGRO100 (G-quadruplex oligodeoxynucleotide) Synthetic NEMO binding Ferry et al., 2002 Ahmed et al., 2005 Rossi et al., 1997, 2000 Oh et al., 2004; Lee et al., 2005e Kim et al., 2006b Kim et al., 2005a Leung et al., 2005 Tabary et al., 2003b Kim et al., 2005c Chaturvedi et al., 1997 Hehner et al., 1998; Whan Han et al., 2001; Schorr et al., 2002 Jang et al., 2005 Manna et al., 1999d; Saliou et al., 1998 Yamamato et al., 1999 Manna & Aggarwal, 2000b; Harada et al., 2005 Sugii et al., 2005 May et al., 2000 Agou et al., 2004 Li et al., 1999 Friedman & Horwitz, 2002 Joo et al., 2005 Spitzovsky et al., 2002 Nichols and Shisler, 2006 Nichols & Shisler, 2006 Choi et al., 2006a Seo et al., 2004 Jarvis et al., 2006 Mehta & Besner, 2003 Min et al., 2005 Bruey et al., 2004 Gustin et al., 2001 Tabary et al., 2003 Oelschlager et al., 2002 Manna et al, 2000 Nakagawa & Akao, 2006 Manna et al., 2000d Kinjyo et al., 2002; Nakagawa et al., 2002 Girvan et al., 2006 4 2-amino-3-cyano-4-aryl-6-(2-hydroxyphenyl)pyridine derivatives Acrolein AS602868 Aspirin, sodium salicylate Synthetic IKK activity Murata et al., 2003 Synthetic Synthetic Synthetic IKK activity IKK activity Phosphorylation, IKK Dihydroxyphenylethanol Epoxyquinone A monomer Inhibitor 22 MLB120 (small molecule) Novel small-molecule inhibitor BMS-345541 CYL-19s and CYL-26z, two synthetic alpha-methylene-gamma-butyrolactone derivatives ACHP (2-amino-6-[2(cyclopropylmethoxy)-6-hydroxyphenyl]4-piperidin-4-yl nicotinonitrile Compound A Synthetic Synthetic Synthetic Synthetic Synthetic Synthetic Synthetic IKK activity IKK/DNA binding IKK activity IKK activity IKK activity IKK activity IKK activity Vallacchi et al., 2005 Frelin et al., 2003 Frantz & O'Neill, 1995; Kopp & Ghosh, 1994; Yin et al., 1998 Guichard et al., 2006 Liang et al., 2006 Baxter et al., 2004 Nagashima et al., 2006 Kamon et al., 2004 Burke et al., 2003 Huang et al., 2004 Synthetic IKK activity (ATP analog) Sanda et al., 2006 Synthetic Ziegelbauer et al., 2005 Compound 5 Cyclopentenones Jesterone dimer Synthetic Synthetic Synthetic PS-1145 (MLN1145) Synthetic 2-[(aminocarbonyl)amino]-5-acetylenyl3-thionphenecarboxamides SC-514 (Amino)imidazolylcarboxaldehyde derivative Amino-pyrimidine Benzoimidazole derivative CDDO-Me (synthetic triterpenoid) CHS 828 (anticancer drug) Diaylpyridine derivative Imidazolylquinoline-carboxaldehyde derivative Indolecarboxamide LF15-0195 (analog of 15deoxyspergualine) ML120B MX781 (retinoid antagonist) NSAIDs N-(4-hydroxyphenyl) retinamide Pyrazolo[4,3-c]quinoline derivative Pyridooxazinone derivative Scytonemin Survanta (Surfactant product) Synthetic IKK activity (ATP analog) IKK activity IKK activity IKK activity; DNA binding IKK activity (ATP analog) IKK activity Synthetic Synthetic IKK activity IKK activity Kishore et al., 2003 Karin et al., 2004 Synthetic Synthetic Synthetic Synthetic Synthetic Synthetic IKK activity IKK activity IKK activity IKK activity IKK activity IKK activity Karin et al., 2004 Karin et al., 2004 Shishodia et al., 2006 Olsen et al., 2004 Murata et al., 2003 Karin et al., 2004 Synthetic Synthetic IKK activity IKK activity Karin et al., 2004 Yang et al., 2003 Synthetic Synthetic Synthetic Synthetic Synthetic Synthetic Synthetic Synthetic IKK activity IKK activity IKK activity IKK activity IKK activity IKK activity IKK activity IKK activity Sulfasalazine Synthetic Sulfasalazine analogs Synthetic IKK and IKK kinase activity IKK kinase activity Catley et al., 2006 Bayon et al., 2003 Takada et al., 2004 Shishodia et al., 2005 Karin et al., 2004 Karin et al., 2004 Stevenson et al., 2002 Raychaudhuri et al., 2003 Wahl et al., 1998: Weber et al., 2000 Habens et al., 2005 Roshak et al., 2002 Bickley et al., 2004 Liang et al., 2003, 2006 Hideshima et al., 2002 Bonafoux et al., 2005 5 Thalidomide Azidothymidine (AZT) Synthetic Synthetic IKK activity Phosphorylation BAY-11-7082 (E3((4-methylphenyl)sulfonyl)-2-propenenitrile) BAY-11-7083 (E3((4-t-butylphenyl)sulfonyl)-2-propenenitrile) Benzyl isothiocyanate Synthetic Phosphorylation Keifer et al., 2001 Ghosh et al., 2003; Kurokawa et al., 2005 Pierce et al., 1997 Synthetic Phosphorylation Pierce et al., 1997 Synthetic Phosphorylation Carboplatin Gabexate mesilate Gleevec (Imatanib) Hydroquinone Ibuprofen Inhaled isobutyl nitrite Methotrexate Synthetic Synthetic Synthetic Synthetic Synthetic Synthetic Synthetic Phosphorylation Phosphorylation Phosphorylation Phosphorylation Phosphorylation Phosphorylation Phosphorylation Monochloramine Nafamostat mesilate Statins (several) Synthetic Synthetic Synthetic Phosphorylation Phosphorylation Phosphorylation THI 52 (1-naphthylethyl-6,7-dihydroxy1,2,3,4- tetrahydroisoquinoline) tetrahydroisoquinoline) 1,2,4-thiadiazolidine derivatives YC-1 Mild hypothermia Synthetic Phosphorylation Srivastava & Singh, 2004 Singh & Bhat, 2004 Uchiba et al., 2003 Wolf et al., 2005 Kerzic et al., 2003 Palayoor et al., 1998 Ponnappan et al., 2004 Majumdar & Aggarwal, 2001; Yozai et al., 2005 Omori et al., 2002 Noguchi et al., 2003 Hilgendorff et al., 2003; Han et al., 2004; Planavila et al., 2005 Kang et al., 2003b Synthetic Synthetic Synthetic - Phosphorylation Phosphorylation Phosphorylation IKK activity Kang et al., 2003b Manna et al., 2004 Huang et al., 2005b Han et al., 2003 Table S3 Inhibitors of IB degradation Molecule Zinc Alachlor Type of molecule Inorganic complex Natural product Point of inhibition Degradation Degradation Amentoflavone Artemisia capillaris Thunb extract Artemisia iwayomogi extract L-ascorbic acid Antrodia camphorata Aucubin Baicalein -lapachone Blackberry extract Buchang-tang Capsaicin (8-methyl-N-vanillyl-6nonenamide) Catalposide Cyclolinteinone (sponge sesterterpene) Dihydroarteanniun Docosahexaenoic acid Emodin (3-methyl-1,6,8- Natural product Natural product Natural product Natural product Natural product Natural product Natural product Natural product Natural product Natural product Natural product Degradation Degradation Degradation Degradation Degradation Degradation Degradation Degradation Degradation Degradation Degradation Natural product Natural product Degradation Degradation Natural product Natural product Natural product Degradation Degradation Degradation References Uzzo et al., 2006 Shimomura-Shimizu et al., 2005 Banerjee et al., 2002 Hong et al., 2004 Kim et al., 2005f Han et al., 2004 Hseu et al., 2005 Jeong et al., 2002 Ma et al., 2004 Manna et al., 1999b Pergola et al., 2006 Shin et al., 2005b Singh et al., 1996; Mori et al., 2006 Kim et al., 2004d D'Acquisto et al., 2000 Li et al., 2006b Weldon et al., 2006 Kumar et al., 1998; 6 trihydroxyanthraquinone) Ephedrae herba (Mao) Equol Erbstatin (tyrosine kinase inhibitor) Estrogen (E2) Natural product Natural product Natural product Natural product Degradation Degradation Degradation Degradation/and various other steps Huang et al., 2004a Aoki et al., 2005 Kang et al., 2005d Natarajan et al., 1998 Sun et al., 1998; Kalaitzidis & Gilmore, 2005; Steffan et al., 2006 Han et al., 2004 Ethacrynic acid Natural product Fosfomycin Natural product Degradation (and DNA binding) Degradation Fungal gliotoxin Gamisanghyulyunbueum Genistein (tyrosine kinase inhibitor) Natural product Natural product Natural product Degradation Degradation Degradation; caspase cleavage of IB Genipin Glabridin Glucosamine sulfate Glutamine Gumiganghwaltang Isomallotochromanol and isomallotochromene Kochia scoparia fruit (methanol extract) Leflunomide metabolite (A77 1726) Natural product Natural product Natural product Natural product Natural product Natural product Degradation Degradation Degradation Degradation Degradation Degradation Yoneshima et al., 2003 Pahl et al., 1999 Shin et al., 2005c Natarajan et al., 1998; Baxa & Yoshimura, 2003 Koo et al., 2004 Kang et al., 2004 Largo et al., 2003 Singleton et al., 2005 Kim et al., 2005d Ishii et al., 2003 Natural product Degradation Shin et al., 2004c Natural product Degradation Melatonin 5'-methylthioadenosine Midazolam Momordin I Mosla dianthera extract Morinda officinalis extract Opuntia ficus indica va saboten extract -Phenylethyl (PEITC) and 8methylsulphinyloctyl isothiocyanates (MSO) (watercress) Platycodin saponins Polymyxin B Poncirus trifoliata fruit extract Probiotics Prostaglandin 15-deoxy-∆(12,14)PGJ(2) Natural product Natural product Natural product Natural product Natural product Natural product Natural product Degradation Degradation Degradation Degradation Degradation Degradation Degradation Manna & Aggarwal, 1999a Zhang et al., 2004c Hevia et al., 2004 Kim et al., 2006g Hwang et al., 2005 Lee et al., 2006a Kim et al., 2005c Lee et al., 2006a Natural product Degradation Rose et al., 2005 Natural product Natural product Natural product Natural product Natural product Degradation Degradation Degradation Degradation Degradation Resiniferatoxin Stinging nettle (Urtica dioica) plant extracts Thiopental Tipifarnib Titanium TNP-470 (angiogenesis inhibitor) Trichomomas vaginalis infection Natural product Natural product Degradation Degradation Natural product Natural product Natural product Natural product Natural product Degradation Degradation Degradation Degradation Degradation Ahn et al., 2005 Jiang et al., 2006 Shin et al., 2006b Petrof et al., 2004 Cuzzocrea et al., 2003; Chatterjee et al., 2004 Singh et al., 1996b Riehemann et al., 1999 Loop et al., 2002 Xue et al., 2005 Yang et al., 2003b Mauriz et al., 2003 Chang et al., 2004 7 Triglyceride-rich lipoproteins Natural product Degradation Ursodeoxycholic acid Xanthium strumarium L. (methanol extract) Penetratin Vasoactive intestinal peptide Natural product Natural product Degradation Degradation Peptide Peptide K1L (Vaccinia virus protein) Nef (HIV-1) Vpu protein (HIV-1) Protein, viral Protein, viral Protein, viral Letoya et al., 2006 Delgado & Ganea, 2001; Delgado, 2002 Shisler & Jin, 2004 Qiao et al., 2006 Bour et al., 2001 -glutamylcysteine synthetase Protein Protein Protein Degradation Degradation (and CBPRelA interaction) Degradation Degradation TrCP ubiquitin ligase inhibitor Degradation Degradation Degradation Protein, bacterial Deubiquintinase for IB Protein Protein Degradation Degradation Protein Degradation Intravenous immunoglobulin Murr1 gene product Neurofibromatosis-2 (NF-2; merlin) protein Pituitary adenylate cyclaseactivating polypeptide (PACAP) SAIF (Saccharomyces boulardii anti-inflammatory factor) Acetaminophen 1-Bromopropane Diamide (tyrosine phosphatase inhibitor) Protein Protein Protein Degradation Degradation Degradation Schesser et al., 1998; Zhou et al., 2005a Yuksel et al., 2002 Manna & Aggarwal, 1998c Manna & Aggarwal, 1998b Ichiyama et al., 2004 Ganesh et al., 2003 Kim et al., 2002 Protein Degradation Protein Degradation Synthetic Synthetic Synthetic Degradation Degradation Degradation Dobutamine E-73 (cycloheximide analog) Ecabet sodium Gabexate mesilate Glimepiride Synthetic Synthetic Synthetic Synthetic Synthetic Degradation Degradation Degradation Degradation Degradation Hypochlorite Losartin LY294002 (PI3-kinase inhibitor) [2-(4-morpholinyl)-8phenylchromone] Pervanadate (tyrosine phosphatase inhibitor) Synthetic Synthetic Synthetic Degradation Degradation Degradation Synthetic Degradation Phenylarsine oxide (PAO, tyrosine phosphatase inhibitor) Synthetic Degradation Phenytoin Synthetic Degradation Heat shock protein-70 ST2 (IL-1-like receptor secreted form) YopJ (encoded by Yersinia pseudotuberculosis) Activated protein C (APC) -melanocyte-stimulating hormone (a-MSH) IL-13 Kumwenda et al., 2002 Joo et al., 2004 Kim et al., 2005b Manna et al., 1999c Chan et al., 2004 Takezako et al., 2006 Delgado & Ganea, 2001 Sougioultzis et al., 2006 Mancini et al., 2003 Yoshida et al., 2006 Toledano & Leonard, 1991; Singh & Aggarwal, 1995a Loop et al., 2004 Sugimoto et al., 2000 Kim et al., 2003a Yuksel et al., 2003 Schiekofer et al., 2003 Mohri et al., 2002 Chen et al., 2002 Park et al., 2002 Singh & Aggarwal, 1995a; Singh et al., 1996a Mahboubi et al., 1998; Singh & Aggarwal, 1995a Kato et al., 2005 8 Sabaeksan U0126 (MEK inhibitor) Ro106-9920 (small molecule) Synthetic Synthetic Synthetic Low level laser therapy Electrical stimulation of vagus nerve - Degradation Degradation IB ubiqutination inhibitor Degradation Degradation Choi et al., 2005 Takaya et al., 2003 Swinney et al., 2002 Rizzi et al., 2006 Guarini et al., 2003 Table S4 Proteasome and protease inhibitors Molecule Lactacystine, -lactone Type of molecule Natural product Point of inhibition Proteasome Cyclosporin A Natural product Proteasome ALLnL (N-acetyl-leucinyl-leucynil-norleucynal, MG101) LLM (N-acetyl-leucinyl-leucynil-methional) Z-LLnV (carbobenzoxyl-leucinyl-leucynilnorvalinal,MG115) Z-LLL (N-carbobenzoxyl-L-leucinyl-L-leucinyl-Lnorleucinal, MG132) Ubiquitin ligase inhibitors Boronic acid peptide Peptide Proteasome Peptide Peptide Proteasome Proteasome Peptide Proteasome Peptides Synthetic Proteasome Proteasome PS-341 (Bortezomib) Synthetic Proteasome Salinosporamide A (1, NPI-0052) Synthetic Proteasome FK506 (Tacrolimus) Synthetic Proteasome Deoxyspergualin Disulfiram Synthetic Synthetic Proteasome Proteasome APNE (N-acetyl-DL-phenylalanine-bnaphthylester) BTEE (N-benzoyl L-tyrosine-ethylester) DCIC (3,4-dichloroisocoumarin) DFP (diisopropyl fluorophosphate) Synthetic Protease Synthetic Synthetic Synthetic Protease Protease Protease References Fenteany & Schreiber, 1998; Grisham et al., 1999 Frantz et al., 1994; Kunz et al., 1995; Marienfeld et al., 1997; McCaffrey et al., 1994; Meyer et al., 1997; Wechsler et al., 1994 Palombella et al., 1994; Jobin et al., 1998; Grisham et al., 1999 Yaron et al., 1997 Iqbal et al., 1995; Grisham et al., 1999 Adams, 2004; Hideshima et al., 2002 Macherla et al., 2005 Okamoto et al., 1994a; Venkataraman et al., 1995 Tepper et al., 1995 Lovborg et al., 2005 Higuchi et al., 1995 Rossi et al., 1998 D'Acquisto et al., 1998 9 TPCK (N--tosyl-L-phenylalanine chloromethyl ketone) TLCK (N--tosyl-L-lysine chloromethyl ketone) Synthetic Protease Synthetic Protease Table S5 IB upregulators, and NF-B nuclear translocation and expression inhibitors Inhibitor molecule Antrodia camphorata extract Apigenin (4',5,7-trihydroxyflavone) Type of molecule Natural product Natural product Point of inhibition IB upregulation IB upregulation Glucocorticoids (dexamethasone, prednisone, methylprednisolone) Natural product IB upregulation Human breast milk Natural product IB upregulation -pinene Agastache rugosa leaf extract Alginic acid Astragaloside IV Atorvastatin 2',8"-biapigenin Natural product Natural product Natural product Natural product Natural product Natural product Blue honeysuckle extract Buthus martensi Karsch extract Chiisanoside Natural product Natural product Natural product 15-deoxyspergualin Natural product IB upregulation Nuclear translocation Nuclear translocation Nuclear translocation Nuclear translocation RelA nuclear translocation Nuclear translocation Nuclear translocation RelA Nuclear translocation Nuclear translocation Eriocalyxin B Gangliosides Harpagophytum procumbens (Devil's Claw) extracts Hirsutenone JM34 (benzamide derivative) Natural product Natural product Natural product Nuclear translocation Nuclear translocation Nuclear translocation Natural product Natural product Nuclear translocation Nuclear translocation KIOM-79 (combined plant extracts) Leptomycin B (LMB) Natural product Natural product Nuclear translocation Nuclear translocation Nucling Natural product o,o'-bismyristoyl thiamine disulfide (BMT) Oregonin Natural product Natural product 1,2,3,4,6-penta-O-galloyl--D-glucose Natural product Platycodi radix extract Natural product Phallacidin Natural product RelA nuclear translocation Nuclear translocation RelA nuclear translocation RelA nuclear translocation RelA nuclear translocation Nuclear translocation Piperine Natural product Nuclear translocation References Hsu et al., 2005 Shukla & Gupta, 2004 Auphan et al., 1995; Brostjan et al., 1996; Ray & Prefontaine, 1994; Scheinman et al., 1995 Minekawa et al., 2004 Zhou et al., 2004 Oh et al., 2005 Jeong et al., 2006 Zhang et al., 2003c Haloui et al., 2003 Woo et al., 2006 Jin et al., 2005 Kim et al., 2005 Won et al., 2005 Hutchings et al., 2003 Wang et al., 2006c Caldwell et al., 2003 Kaszkin et al., 2004 Kim et al., 2005c Carbonnelle et al., 2005 Jeon et al., 2006 Rodriguez et al., 1999 Liu et al., 2004 Shoji et al., 1998 Lee et al., 2005a Kang et al., 2005b Lee et al., 2004c Papakonstanti & Strounaras, 2004 Pradeep & Kuttan, 2004 10 Pitavastatin Probiotics Natural product Natural product Rhubarb aqueous extract Natural product Selenomethionine Natural product Salvia miltiorrhoza Bunge extract ShenQi compound recipe Natural product Natural product Sophorae radix extract Sopoongsan Sphondin (furanocoumarin derivative from Heracleum laciniatum) Younggaechulgam-tang Clarithromycin Natural product Natural product Natural product 5F (from Pteri syeminpinnata L)) AT514 (serratamolide) Natural product Natural product Nuclear translocation Nuclear NF-B expression RelA expression RelA expression oxidized 1-palmitoyl-2-arachidonoyl-snglycero-3-phosphorylcholine (OXPAPC) Sorbus commixta cortex (methanol extract) Cantharidin Cornus officinalis extract Neomycin Natural product RelA expression Natural product Natural product Natural product Natural product RelA expression NF-B expression NF-B expression NF-B expression Paeoniflorin Rapamycin Natural product Natural product NF-B expression NF-B expression Sargassum hemiphyllum methanol extract Shenfu Tripterygium polyglycosides PN50 Cell permeable NLS peptides RelA peptides (P1 and P6) Canine Distemper Virus MNF (myxoma virus) Natural product Natural product Natural product Peptide Peptide Peptide Protein, viral Protein, viral NF-B expression NF-B expression NF-B expression Nuclear translocation Nuclear translocation Nuclear translocation Nuclear translocation Nuclear translocation 3C protease (encephalomyocarditis virus) Protein, viral Rel A expression ZUD protein Protein HSCO (hepatoma protein) Protein -amyloid protein Surfactant protein A (SP-A) DQ 65-79 (aa 65-79 of the alpha helix of the alpha-chain of the class II HLA molecule DQA03011) C5a Protein Protein Protein Activation of NF-B; binds p105/RelA Accelerates RelA nuclear export IB upregulation IB upregulation IB upregulation and IKK inhibition Protein IB upregulation IL-10 Protein IB upregulation Natural product Natural product Nuclear translocation RelA nuclear translocation RelA nuclear translocation Nuclear translocation Nuclear translocation RelA nuclear translocation Nuclear translocation Nuclear translocation Nuclear translocation Wang et al., 2006a Bai et al., 2004 Moon et al., 2005 Cherukuri et al., 2005 Ding et al., 2005 Zhang et al., 2006 Kwon et al., 2004 Na et al., 2005 Yang et al., 2002 Shin et al., 2004b Ichiyama et al., 2001 He et al., 2005a Escabar-Diaz et al., 2005 Li et al., 2004a Sohn et al., 2005 He et al., 2005b Li et al., 2005a Garcia-Trapero et al., 2004 Liu et al., 2006b Lawrence et al., 2004 Na et al., 2005 Zhang et al., 2005 Zhou et al., 2005b Letoha et al., 2005 Lin et al., 1995 Takada et al.., 2004c Friess et al., 2005 Camus-Bouclainville et al., 2004 Neznanov et al., 2005 Zhang et al., 2004b Higashitsuji et al., 2002 Bales et al., 1998 Wu et al., 2004c Jiang et al., 2002 Riedemann et al., 2003 Ehrlich et al., 1998; Lentsch et al., 1997; 11 IL-11 Protein IKK; IB,IB upregulation IL-13 Protein IB upregulation Fox1j Glucorticoid-induced leucine zipper protein (GILZ) Heat shock protein 72 Retinoic acid receptor-related orphan receptor-alpha TAT-SR- IB; MTS-SR-IB; p105-SR Protein Protein IB upregulation Nuclear translocation Shames et al., 1998 Trepicchio & Dorner, 1998; Lgssiar et al., 2004 Ehrlich et al., 1998; Lentsch et al., 1997; Manna & Aggarwal, 1998b Lin et al., 2004 Riccardi et al., 2001 Protein Protein Nuclear translocation Nuclear translocation Meldrum et al., 2003 Migita et al., 2004 Protein Nuclear translocation ZAS3 protein Protein RASSF1A gene overexpression Protein Onconase (Ranpirnase) R-etodolac BMD (N(1)-Benzyl-4-methylbenzene-1,2diamine) Carbaryl Protein Synthetic Synthetic RelA nuclear translocation; DNA competition RelA nuclear expression NF-B expression IB upregulation Nuclear translocation Blackwell et al., 2004; Fu et al., 2004; Mora et al., 2005 Hong et al., 2003 Synthetic Nuclear translocation Indole-3-carbinol Synthetic Nuclear translocation Dioxin Synthetic Dehydroxymethylepoxyquinomicin (DHMEQ) Dipyridamole Disulfiram Diltiazem Synthetic RelA nuclear translocation Nuclear translocation Fluvastatin JSH-23 (4-Methyl- -(3-phenyl-propyl)benzene-1,2-diamine KL-1156 (6-Hydroxy-7-methoxychroman-2carboxylic acid phenylamide) Leflunomide Synthetic Synthetic Nuclear translocation Nuclear translocation Nuclear translocation; induced translocation of p50 dimers Nuclear expression Nuclear translocation Synthetic Nuclear translocation Kim et al., 2004a Synthetic Yao et al., 2004 Levamisole MEB (2-(4-morpholynl) ethyl butyrate hydrochloride) Rolipram Synthetic Synthetic RelA nuclear expression Nuclear translocation Nuclear translocation Synthetic Nuclear translocation SC236 (a selective COX-2 inhibitor) Triflusal Volatile anesthetic treatment Synthetic Synthetic Synthetic Nuclear translocation Nuclear expression Nuclear translocation Synthetic Synthetic Synthetic Deng et al., 2005 Tsai et al, 2004 Neri et al., 2006 Shin et al., 2005a Shimomura-Shimizu et al., 2005 Rahman & Sarkar, 2005 Ruby et al., 2002 Chaicharoenpong et al., 2002 Weyrich et al., 2005 Wang et al., 2003 Severa et al., 2005 Azuma et al., 2004 Shin et al., 2004 Liu et al., 2004a Soderberg et al., 2004 Sanchez et al., 2005; Ikezoe et al., 2004 Wong et al., 2003 Acarin et al., 2000 Lee et al., 2004b 12 Moxifloxacin Omapatrilat, enalapril, CGS 25462 Estrogen enhanced transcript Synthetic Synthetic mRNA RelA expression NF-B expression Nuclear translocation Werber et al., 2005 Pu et al., 2005 Jin et al., 2003 Table S6 NF-B DNA-binding inhibitors Molecule Metals (chromium, cadmium, gold, lead, mercury, zinc, arsenic) Type of molecule Inorganic Complex Point of inhibition DNA binding References Shumilla et al., 1998; Yang et al., 1995; Zuscik et al., 2002 Hsieh et al., 2004 Actinodaphine (from Cinnamomum insularimontanum) Anthocyanins (soybean) Arnica montana extract (sequiterpene lactones) Artemisinin Natural product DNA binding Natural product Natural product Natural product DNA binding DNA binding DNA binding Baicalein (5,6,7-trihydroxyflavone) Bambara groundnut (Vignea subterranean) -lapachone (1,2-naphthoquinone) Biliverdin Natural product Natural product Natural product Natural product DNA binding DNA binding DNA binding DNA binding Brazilian Calcitriol (1a,25-dihydroxyvitamin D3) Campthothecin Cancer bush (Sutherlandia frutescens) Capsiate Catalposide (stem bark) Cat's claw bark (Uncaria tomentosa; Rubiaceae); Maca Natural product Natural product Natural product Natural product Natural product Natural product Natural product DNA binding DNA binding DNA binding DNA binding DNA binding DNA binding DNA binding Cheongyeolsaseuptang Chitosan Chicory root (guaianolide 8-deoxylactucin) Chondrotin sulfate proteoglycan degradation product Clarithromycin Natural product Natural product Natural product Natural product DNA binding DNA binding DNA binding DNA binding Natural product DNA binding Cloricromene Compound K (from Panax ginseng) Cortex cinnamomi extract Cryptotanshinone Cytochalasin D DA-9201 (from black rice) Danshenshu Diterpenoids from Isodon rubescens or Liverwort Jungermannia ent-kaurane diterpenoids (Croton tonkinensis leaves) Epinastine hydrochloride Epoxyquinol A (fungal metabolite) Erythromycin Natural product Natural product Natural product Natural product Natural product Natural product Natural product Natural product DNA binding DNA binding DNA Binding DNA binding DNA binding DNA binding DNA binding DNA binding Natural product DNA binding Miyanohara et al., 2000 Ianaro et al., 2004 Park et al., 2005a Kwon et al., 2006 Zhou et al., 2006 Kim et al., 2003d Lee et al., 2005e Jiang et al., 2001 Leung et al., 2005; Kondoh et al., 2005 Giang et al., 2003 Natural product Natural product Natural product Evodiamine Natural product DNA binding DNA binding DNA binding/ transactivation DNA binding Kanai et al., 2006 Li et al., 2002 Ren et al., 2004; Desaki et al., 2004 Choi et al., 2006b Kim et al., 2006a Kos et al., 2005 Aldieri et al., 2003; Wang et al., 2006b Suk et al., 2003 Na et al., 2004 Tzeng et al., 2003 Yamashita et al., 2004 Bae et al., 2005 Harant et al., 1998 Hentze et al., 2004 Na et al., 2004 Sancho et al., 2002 Oh et al., 2002 Aguilar et al., 2002; Valerio & Gonzales, 2005 Kim et al., 2005i Seo et al., 2003 Cavin et al., 2005 Rolls et al., 2006 13 Fish oil feeding Fomes fomentarius methanol extracts Fucoidan Gallic acid Ganoderma lucidum (fungal dried spores or fruting body) Garcinol (fruit rind of Garcinia spp) Geranylgeraniol Natural product Natural product Natural product Natural product Natural product DNA binding DNA binding DNA binding DNA binding DNA binding Fan et al., 2004 Park et al., 2004b Haneji et al., 2005 Kim et al., 2005f Sliva et al., 2002 Natural product Natural product DNA binding DNA binding Ginkgolide B Glycyrrhizin Halofuginone Hematein (plant compound) Herbal compound 861 Hydroxyethyl starch Natural product Natural product Natural product Natural product Natural product Natural product DNA binding DNA binding DNA binding DNA binding DNA binding DNA binding Hydroxyethylpuerarin Hypericin Kamebakaurin Linoleic acid Lithospermi radix Macrolide antibiotics Mediterranean plant extracts 2-methoxyestradiol Natural product Natural product Natural product Natural product Natural product Natural product Natural product Natural product 6-(Methylsulfinyl)hexyl isothiocyanate (Wasabi) Nicotine Ochna macrocalyx bark extracts Oridonin (diterpenoid from Rabdosia rubescens) PC-SPES (8 herb mixture) Natural product DNA binding DNA binding DNA binding DNA binding DNA binding DNA binding DNA binding DNA binding; transactivation DNA binding; transactivation DNA binding DNA binding DNA binding DNA binding Hong et al., 2005 de Moura Espindola et al., 2005 Nie et al., 2004 Wang et al., 1998 Leiba et al., 2006 Oh et al., 2001 You et al., 2001 Tian et al., 2003; Feng et al., 2006 Lou et al., 2004 Bork et al., 1999 Lee et al., 2002b Zhao et al., 2005 Chung et al., 2005 Nguyen et al., 2002 Stalinska et al., 2005 Shimada et al., 2004; Takata et al., 2004 Uto et al., 2005 1,2,3,4,6-penta-O-galloyl--D-glucose Pepluanone Phyllanthus amarus extracts Plant compound A (a phenyl aziridine precursor) Polyozellin Prenylbisabolane 3 Natural product Natural product Natural product Natural product Prostaglandin E2 Natural product Protein-bound polysaccharide (PSK) Quinic acid Sanggenon C Sesamin (from sesame oil) Shen-Fu Silibinin Natural product Natural product Natural product Natural product Natural Product Natural product DNA binding and RelA nuclear translocation DNA binding DNA binding DNA binding DNA binding DNA binding DNA binding Sinomenine Sword brake fern extract Tanacetum larvatum extract Tansinones (Salvia miltiorrhiza Bunge, Labiatae Natural product Natural product Natural product Natural product DNA binding DNA binding DNA binding DNA binding Natural product Natural product Natural product Natural product Natural product Natural product DNA binding DNA binding DNA binding DNA binding and transactivation DNA binding DNA binding Sugano et al., 1998 Tang et al., 2003 Ikezoe et al., 2005 Ikezoe et al., 2003; 2006 Oh et al., 2001 Corea et al., 2005 Kiemer et al., 2003 De Bosscher et al., 2005 Jin et al., 2006 Campagnuoloe et al., 2005 Min et al., 2002; Gomez et al., 2005 Zhang et al., 2003a Akesson et al., 2005 Li et al., 2002 Jeng et al., 2005 Qian et al., 2006 Schumann et al., 2003 Chen et al., 2004b Wu et al., 2003 Petrovic et al., 2003 Choi et al., 2004b 14 roots) Taurine + niacine Natural product DNA binding Thiazolidinedione MCC-555 Natural product DNA binding Trichostatin A Triptolide (PG490, extract of Chinese herb) Natural product Natural product RelA DNA binding DNA binding Tyrphostin AG-126 Ursolic acid Withaferin A Xanthohumol (a hops prenylflavonoid) Xylitol Yan-gan-wan Yin-Chen-Hao Yucca schidigera extract Natural product Natural product Natural product Natural product Natural product Natural product Natural product Natural product DNA binding DNA binding DNA binding DNA binding DNA binding DNA binding DNA binding DNA binding Ghrelin Peptide YY Peptide Peptide DNA binding DNA binding Rapamycin A238L IB-like protein (African Swine Fever virus) C + V proteins (Sendai virus) E1B (Adenovirus) Peptide Protein, viral DNA binding DNA binding Protein, viral Protein, viral DNA binding DNA binding ICP27 (Herpes simplex virus-1) Protein, viral DNA binding H4/N5 (Microplitis demolitor bracovirus) Protein, viral DNA binding NS3/4A (Hepatitis C) Adiponectin Protein, viral Protein DNA binding DNA binding AIM2 (Absent in melanoma protein) overexpression Angiopoietin-1 Antithrombin Protein DNA binding Protein Protein AvrA protein (Salmonella) Protein DNA binding RelA-p300 interaction DNA binding -catenin Protein Protein Protein DNA binding DNA binding DNA binding Protein Protein Protein DNA binding (RelA) DNA binding DNA binding G-120 (Ulmus davidiana Nakai glycoprotein) Protein Gax (homeobox protein) Protein DNA binding; IB increases DNA binding Bromelain Calcium/calmodulin-dependent kinase kinase (CaMKK) (and increased intracellular calcium by ionomycin, UTP and thapsigargin) CD43 overexpression FLN29 overexpression FLICE-Like Inhibitory Protein (FLIP) Giri, 2003; Kim & Kim, 2005 Kurebayashi et al., 2005 Hu & Colburn, 2005 Qiu et al., 1999; Kim et al., 2004e; Yinjun et al., 2005 Moore et al., 2003 Hsu et al., 2004 Mohan et al., 2004 Colgate et al., 2006 Han et al., 2005a Yang et al., 2005a Cai et al., 2006 Marzocco et al., 2004; Cheeke et al., 2006 Li et al., 2004b Vona-Davis et al., 2004 Dichtl et al., 2005 Powell et al., 1996; Revilla et al., 1998 Komatsu et al., 2004 Limbourg et al., 1996 Melchjorsen et al., 2006 Thoetkiattikul et al., 2005 Karayiannis, 2005 Ajuwon & Spurlock, 2005 Chen et al., 2006a Jeon et al., 2003 Uchiba et al., 2004 Collier-Hyams et al., 2002 Deng et al., 2002 Hou et al., 2006 Chen et al., 2002d Laos et al., 2004 Mashima et al., 2005 Bannerman et al., 2004 Son et al., 2004b; Lee et al., 2005d Patel et al., 2005 15 HIV-1 Resistance Factor Insulin-like growth factor binding protein-3 Interleukin 4 (IL-4) Protein Protein Protein DNA binding DNA binding DNA binding Leucine-rich effector proteins of Salmonella & Shigella (SspH1 and IpaH9.8) NDPP1 (CARD protein) Overexpressed ZIP1 p8 p202a (nterferon inducible protein) Protein DNA binding Protein Protein Protein Protein p21 (recombinant) PIAS1 (protein inhibitor of activatated STAT1) Pro-opiomelanocortin PYPAF1 protein Raf Kinase Inhibitor Protein (RKIP) Rhus verniciflua Stokes fruits 36 kDa glycoprotein Secretory leucoprotease inhibitor (SLPI) Protein Protein Protein Protein Protein Protein DNA binding DNA binding DNA binding DNA binding by p65 and p50/p65; increases p50 DNA binding RelA DNA binding DNA binding DNA binding DNA binding DNA binding Protein DNA binding Siah2 SIRT1 Deacetylase overexpression Siva-1 Solana nigrum L. Protein Protein Protein Protein DNA binding DNA binding DNA binding DNA binding Surfactant protein A Protein DNA binding Tom1 (target of Myb-1) overexpression Protein DNA binding Transdominant p50 Uteroglobin Vascular endothelial growth factor (VEGF) Protein Protein Protein DNA binding DNA binding DNA binding ADP ribosylation inhibitors (nicotinamide, 3aminobenzamide) 7-amino-4-methylcoumarin Synthetic DNA binding Synthetic DNA binding Amrinone Atrovastat (HMG-CoA reductase inhibitor) Synthetic Synthetic DNA binding DNA binding Benfotiamine (thiamine derivative) Bisphenol A Caprofen Carbocisteine Celecoxib and germcitabine Cinnamaldehyde, 2-methoxycinnamaldehyde, 2-hydroxycinnamaldehyde Commerical peritoneal dialysis solution Synthetic Synthetic Synthetic Synthetic Synthetic Synthetic DNA binding DNA binding DNA binding DNA binding DNA binding DNA binding Synthetic DNA binding CP Compound (6-Hydroxy-7-methoxychroman- Synthetic DNA binding Lesner et al., 2005 Williams et al., 2006 Manna & Aggarwal, 1998a Haraga & Miller, 2003 Zhang & Fu, 2002 Khadeer et al., 2005 Vasseur et al., 2004 Ma et al., 2003 Khanna et al., 2005 Liu et al., 2005a Liu et al., 2006a Jeru et al., 2006 Keller, 2004 Ko et al., 2005 Jin et al., 1997: Greene et al., 2004; Taggart et al., 2005 Habelhah et al., 2002 Chen et al., 2005a Gudi et al., 2006 Heo et al., 2004; Lee & Lim, 2006 Alcorn & Wright, 2003 Yamakami & Yokosawa, 2004 Logeat et al., 1991 Mandal et al., 2004 Oyama et al., 1998; Gabrilovich et al., 1998 Le Page et al., 1998 Kurokawa et al., 2003 Chanani et al., 2002 Bustos et al., 1998; Hernandez-Presa et al., 1998 Hammes et al., 2003 Kim & Jeong, 2003 Bryant et al., 2003 Yasuda et al., 2006 El-Rayes et al., 2004 Reddy et al., 2004; Lee et al., 2005f Douvdevani et al., 1995 Rak Min et al., 2005 16 2-carboxylic acid phenylamide) Cyanoguanidine CHS 828 (B site) Decoy oligonucleotides Diarylheptanoid 7-(4'-hydroxy-3'methoxyphenyl)-1-phenylhept-4-en-3-one -difluoromethylornithine (polyamine depletion) DTD (4,10-dichloropyrido[5,6:4,5]thieno[3,2d':3,2- d]-1, 2, 3-ditriazine) Evans Blue Evodiamine Fenoldopam Synthetic Synthetic Synthetic DNA binding DNA binding DNA binding Johanson et al., 2006 Kupatt et al., 2002 Yadav et al., 2003 Synthetic DNA binding Facchini et al., 2005 Synthetic DNA binding Rioja et al., 2002 Synthetic Synthetic Synthetic DNA binding DNA binding DNA binding Fexofenadine hydrochloride Fibrates FK778 Flunixin meglumine Flurbiprofen Hydroquinone (HQ) IMD-0354 Synthetic Synthetic Synthetic Synthetic Synthetic Synthetic Synthetic DNA binding DNA binding DNA binding DNA binding DNA binding DNA binding DNA binding JSH-21 (N1-Benzyl-4-methylbenzene-1,2diamine) KT-90 (morphine synthetic derivative) Lovastatin Synthetic DNA binding Sharma et al., 2004 Takada et al., 2005a Aravindan et al., 2006 Asano et al., 2004 Hirano et al., 2002 Zeyda et al., 2005 Bryant et al., 2003 Fratelli et al., 2003 Pyatt et al., 1998 Tanaka et al., 2004, 2006 Min et al., 2004 Synthetic Synthetic DNA binding DNA binding Mercaptopyrazine Mevinolin, 5'-methylthioadenosine (MTA) Monomethylfumarate Moxifloxacin Nicorandil Synthetic Synthetic Synthetic Synthetic Synthetic DNA binding DNA binding DNA binding DNA binding DNA binding Nilvadipine Nitric oxide-donating aspirin Synthetic Synthetic DNA binding DNA binding Panepoxydone Peptide nucleic acid-DNA decoys Perindopril 6(5H)-phenanthridinone and benzamide Phenyl-N-tert-butylnitrone (PBN) Pioglitazone (PPARgamma ligand) Pirfenidone Synthetic Synthetic Synthetic Synthetic Synthetic Synthetic Synthetic DNA binding DNA binding DNA binding DNA binding DNA binding DNA binding DNA binding Pyridine N-oxide derivatives Quinadril (ACE inhibitor) Synthetic Synthetic DNA binding DNA binding Raloxifene Raxofelast Ribavirin Rifamides Ritonavir Rosiglitazone Synthetic Synthetic Synthetic Synthetic Synthetic Synthetic RelA DNA binding DNA binding DNA binding DNA binding DNA binding DNA binding Sueoka et al., 1998 Sun & Fernandes, 2003 Lim et al., 2004 Law et al., 1992 Litjens et al., 2004 Werber et al., 2005 Katamura et al., 2005 Iwasaki et al., 2005 Kashfi & Rigas, 2005 Erkel et al., 1996 Penolazzi et al., 2004 Li et al., 2005 Chiarugi, 2002 Kotake et al., 1998 Takagi et al., 2002 Tsuchiya et al., 2004; Nakanishi et al., 2004 Stevens et al., 2006 Bustos et al., 1998; Hernandez-Presa et al., 1998 Olivier et al., 2006 Altavilla et al., 2003 Fiedler et al., 1996 Pahlevan et al., 2002 Ikezoe et al., 2004 Gruden et al., 2005 17 Roxithromycin Santonin diacetoxy acetal derivative Serotonin derivative (N-(p-coumaroyl) serotonin, SC) Simvastatin Synthetic Synthetic Synthetic DNA binding DNA binding DNA binding Synthetic DNA binding SM-7368 (small molecule) T-614 (a methanesulfoanilide anti-arthritis inhibitor) Sulfasalazine Synthetic Synthetic DNA binding DNA binding Synthetic DNA binding SUN C8079 Synthetic DNA binding Triclosan plus cetylpyridinium chloride Tobacoo smoke Verapamil Heat (fever-like) Hypercapnic acidosis Synthetic Synthetic Synthetic - DNA binding DNA binding DNA binding DNA binding DNA binding Hyperosmolarity Hypothermia Moderate alcohol intake - DNA binding DNA binding DNA binding Kim et al., 2004 Kim et al., 2006 Kawashima et al., 1998 Li et al., 2002; Kalyanasundaram et al., 2006 Lee et al., 2005 Aikawa et al., 2002 Egan & Sandborn, 1998 Matsumori et al., 2004 Kim et al., 2005 Zhong et al., 2006 Li et al., 2006 Salanova et al., 2005 Ni Chonghaile et al., 2005 Lang et al., 2003 Hassoun et al., 2003 Mandrekar et al., 2006 Table S7 NF-B transactivation inhibitors Molecule 8-acetoxy-5-hydroxyumbelliprenin Type of molecule Natural product Point of Inhibition Transactivation Adenosine and cyclic AMP Natural product Transactivation Artemisia sylvatica sesquiterpene lactones Natural product -zearalenol Natural product Natural product Natural product (Bacteria) Natural product Natural product Natural product Transactivation (reporter assays) Transactivation Transactivation Transactivation BSASM (plant extract mixture) Bifodobacteria Bupleurum fruticosum phenylpropanoids Blueberry and berry mix (Optiberry) 4'-demethyl-6-methoxypodophyllotoxin (lignan of Linum tauricum Willd. ssp. tauricum) Cycloprodigiosin hycrochloride Eckol/Dieckol (seaweed E stolonifera) Extract of the stem bark of Mangifera indica L. Fructus Benincasae Recens extract Glucocorticoids (dexametasone, prednisone, methylprednisolone) Natural product Natural product Natural product Natural product Natural product References Appendino et al., 2006 Majumdar & Aggarwal, 2003; Minguet et al., 2004 Jin et al., 2004 Li et al., 2005 Lee et al., 2005 Riedel et al., 2006 Transactivation Transactivation Transactivation Bremner et al., 2004 Atalay et al., 2003 Vailev et al., 2005 Transactivation Transactivation NF-B mRNA expression Transactivation Transactivation and increases IB levels Kamata et al., 2001 Joe et al.., 2006 Leiro et al., 2004 Kwon et al., 2003 Auphan et al., 1995; Brostjan et al., 1996; 18 Gypenoside XLIX (from Gynostemma pentaphyllum) Kwei Ling Ko (Tortoise shell-Rhizome jelly) Ligusticum chuanxiong Hort root Luteolin Manassantins A and B Natural product Ray & Prefontaine,1994; Scheinman et al., 1995 Huang et al., 2006 Natural product Transactivation (PPAR-dependent) Transactivation Natural product Natural product Natural product Transactivation P65 transactivation RelA transactivation Mesuol Natural product Nobiletin Natural product RelA phosphorylation & transactivation Transactivation 4-phenylcoumarins (from Marila pluricostata) Phomol Psychosine Qingkailing and Shuanghuanglian (Chinese medicinal preparations) Saucerneol D and saucerneol E Smilax bockii warb extract (flavenoids) Trilinolein Uncaria tomentosum plant extract Witheringia solanacea leaf extracts Natural product Transactivation Murakami et al., 2005 Bedoya et al., 2005 Natural product Natural product Natural product Transactivation Transactivation Transactivation Weber et al., 2004 Haq et al., 2003 Chen et al., 2002a Natural product Natural product Natural product Natural product Natural product Transactivation Transactivation Transactivation Transactivation Transactivation Wortmannin (fungal metabolite) Natural product Transactivation BZLF1 (EBV protein) Protein, viral Transactivation SH gene products (Paromyxovirus) NRF (NF-B repression factor) PIAS3 PTX-B (pertussis toxin binding protein) Protein, viral Protein Protein Protein Antithrombin 17-allylamino-17-demethoxygeldanamycin 6-aminoquinazoline derivatives Chromene derivatives D609 (phosphatidylcholine-phospholipase C inhibitor) Dimethylfumarate (DMF) Ethyl 2-[(3-methyl-2,5-dioxo(3pyrrolinyl)) pyrimidine-5-carboxylate pyrimidine-5-carboxylate Histidine HIV-1 protease inhibitors (nelfinavir, ritonavir, or saquinavir) Phenethylisothiocyanate Protein Synthetic Synthetic Synthetic Synthetic Transactivation Transactivation Transactivation RelA phosphorylation and transactivation RelA-p300 interaction Transactivation Transactivation Transactivation Transactivation Synthetic Synthetic Nuclear translocation Transactivation Hwang et al., 2003 Xu et al., 2005 Liu et al., 2004b Akesson et al., 2003 Jacobo-Herrera et al., 2006 Reddy et al., 1997; Manna & Aggarwal, 2000a Morrison et al., 2004 Wilson et al., 2006 Jianfeng et al., 2004 Jang et al., 2004 Iordanskiy et al., 2002 Uchiba et al., 2004 Rakitina et al., 2003 Tobe et al., 2003 Cheng et al., 2003 Bergmann et al., 1998 Loewe et al., 2002 Palanki et al., 2002 Synthetic Synthetic Transactivation Transactivation Son et al., 2005a Equils et al., 2004 Synthetic Transactivation Pranlukast Synthetic Transactivation Gerhauser et al., 2003 Ichiyama et al., Yip et al., 2005 Liu et al., 2005 Kim et al., 2003 Lee et al., 2003; Son et al., 2005 Marquez et al., 2005 19 RO31-8220 (PKC inhibitor) Synthetic Transactivation SB203580 (p38 MAPK inhibitor) Synthetic Transactivation Tetrathiomolybdate Tranilast [N-(3,4dimethoxycinnamoyl)anthranilic acid] 3,4,5-trimethoxy-4'-fluorochalcone Troglitazone 9-aminoacridine (9AA) derivatives (including the antimalaria drug quinacrine) Mesalamine Synthetic Synthetic Transactivation Transactivation Synthetic Synthetic Synthetic Low gravity - Transactivation Transactivation RelA phosphorylation and transactivation RelA phosphorylation & transactivation Transactivation Synthetic 2003; Ishinaga et al., 2004 Bergmann et al., 1998 Bergmann et al., 1998 Pan et al., 2002 Spiecker et al., 2002 Rojas et al., 2003 Ruan et al., 2003 Gurova et al., 2005 Egan et al., 1999 Boonyaratanakornkit et al., 2005 Table S8 Antioxidants Molecule Aged garlic extract (allicin) 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) Anetholdithiolthione Apocynin Apple juice/extracts Aretemisa p7F (5,6,3',5'-tetramethoxy 7,4'hydroxyflavone) Astaxanthin Benidipine bis-eugenol Bruguiera gymnorrhiza compounds Butylated hydroxyanisole (BHA) Caffeic Acid Phenethyl Ester (3,4-dihydroxycinnamic acid, CAPE) Carnosol -Carotene Carvedilol Catechol derivatives Celasterol Cepharanthine Chlorophyllin Chlorogenic acid Cocoa polyphenols Curcumin (Diferulolylmethane) Dehydroevodiamine References Ide & Lau, 2001; Lang et al., 2004 Yun et al., 2005 Sen et al., 1996 Barbieri et al., 2004 Shi & Jiang, 2002; Davis et al., 2006 Lee et al., 2004a Lee et al., 2003d Matsubara & Hazegawa, 2004 Murakami et al., 2003 Homhual et al., 2006 Isral et al., 1992; SchulzeOsthoff et al., 1993 Natarajan et al., 1996 Lo et al., 2002; Huang et al., 2005a Bai et al., 2005 Yang et al., 2003 Suzuki & Packer, 1994 Pinna et al., 2004 Okamoto et al., 1994 Yun et al., 2005 Feng et al., 2005 Lee et al., 2006f Singh & Aggarwal, 1995 Noh et al., 2006 20 Dehydroepiandrosterone (DHEA) and sulfate (DHEAS) Dibenzylbutyrolactone lignans Diethyldithiocarbamate (DDC) Diferoxamine DHEA- Dihydroisoeugenol Dihydrolipoic acid Dilazep + fenofibric acid Dimethyldithiocarbamates (DMDTC) Dimethylsulfoxide (DMSO) Disulfiram Ebselen Edaravone EPC-K1 (phosphodiester compound of vitamin E and vitamin C) Epigallocatechin-3-gallate (EGCG; green tea polyphenols) Ergothioneine Ethyl pyruvate (glutathione depletion) Ethylene glycol tetraacetic acid (EGTA) Extract of the stem bark of Mangifera indica L. Flavonoids (Crataegus; Boerhaavia diffusa root; xanthohumol) Gamma-glutamylcysteine synthetase (gamma-GCS) Ganoderma lucidum polysaccharides Garcinol (from extract of Garcinia indica fruit rind) Ginkgo biloba extract Glutathione Hematein Hydroquinone 23-hydroxyursolic acid IRFI 042 (Vitamin E-like compound) Iron tetrakis Isovitexin Kangen-karyu extract Ketamine L-cysteine Lacidipine Lazaroids Ligonberries -lipoic acid Lupeol Magnolol Maltol Manganese superoxide dismutase (Mn-SOD) Mangiferin Iwasaki et al., 2004; Liu et al., 2005c Cho et al., 2002 Schreck et al., 1992b Sappey et al., 1995; Schreck et al., 1992a Murakami et al., 1995 Suzuki et al., 1992, 1995 Sonoki et al., 2003; Yang et al., 2005b Pyatt et al., 1998a Kelly et al., 1994 Schreck et al., 1992a Schreck et al., 1992a Kokura et al., 2005 Hirano et al., 1998 Lin & Lin, 1997; Yang et al.,1998 Rahman et al., 2003 Song et al., 2004; Tsung et al., 2005 Janssen et al., 1999 Leiro et al., 2004; Garrido et al., 2005 Zhang et al., 2004a; Chen et al., 2004a; Pandey et al., 2005; Albini et al., 2005; Colgate et al., 2006 Manna et al., 1999c Zhang et al., 2003b Liao et al., 2004 Chen et al., 2003 Cho et al., 1998; Schreck et al., 1992a Choi et al., 2003 Pyatt et al., 1998b Shin et al., 2004c Altavilla et al., 2001 Kang et al., 2001 Lin et al., 2005 Satoh et al., 2005 Sun et al., 2004 Mihm et al., 1991 Cominacini et al., 1997 Marubayashi et al., 2002 Wang et al., 2005a Suzuki et al., 1992; Sen et al., 1998 Saleem et al., 2004 Chen et al., 2002d Yang et al., 2006 Manna et al., 1998d Leiro et al., 2004 21 Melatonin Mulberry anthocyanins Myricetin Naringin N-acetyl-L-cysteine (NAC) Nacyselyn (NAL) N-ethyl-maleimide (NEM) Nitrosoglutathione Nordihydroguaiaritic acid (NDGA) Ochnaflavone Orthophenanthroline PMC (2,2,5,7,8-pentamethyl-6-hydroxychromane) Pentoxyifylline (1-(5’-oxohexyl) 3,7dimehylxanthine, PTX) Phenolic antioxidants (Hydroquinone and tert-butyl hydroquinone) Phenylarsine oxide (PAO, tyrosine phosphatase inhibitor) Phyllanthus urinaria Pyrithione Pyrrolinedithiocarbamate (PDTC) Quercetin (low concentrations) Quinozolines Rebamipide Red wine Ref-1 (redox factor 1) Resveratrol Rg(3), a ginseng derivative Rotenone Roxithromycin S-allyl-cysteine (SAC, garlic compound) Sauchinone Spironolactone Strawberry extracts Taxifolin Tempol Tepoxaline (5-(4-chlorophenyl)-N-hydroxy-(4methoxyphenyl) -N-methyl-1H-pyrazole-3propanamide) Tetracylic A Gilad et al., 1998; Mohan et al., 1995; Li et al., 2005c Chen et al., 2005b Kuo et al., 2004; Khan et al., 2005 Kanno et al., 2005 Schreck et al., 1991 Antonicelli et al., 2002 Toledano and Leonard, 1991 Kuo et al., 2004; Khan et al., 2005 Brennan & O'Neill, 1998; Israel et al.,1992; Schulze-Osthoff et al., 1993; Staal et al., 1993 Suh et al., 2006 Schreck et al., 1992a Suzuki & Packer, 1993 Biswas et al., 1993; Wang et al., 1997; Ji et al., 2004 Ma et al., 2003 Arbault et al., 1998 Chularojmontri et al., 2005 Kim et al., 1999 Schreck et al., 1992b Musonda & Chipman, 1998; Shih et al., 2004 Tobe et al., 2003 Hahm et al., 2003 Blanco-Colio et al., 2000; Cui & He, 2004 Ozaki et al., 2002 Manna et al., 2000; Pendurthi et al., 2002 Keum et al., 2003 Schulze-Osthoff et al., 1993 Ueno et al., 2005 Geng et al., 1997 Lee et al., 2003a; Hwang et al., 2003 Han et al., 2006 Wang et al., 2005b Wang et al., 2006d Cuzzocrea et al., 2004 Kazmi et al., 1995; Ritchie et al., 1995 Liu et al., 2004b 22 -tocopherol -torphryl acetate -torphryl succinate Vitamin C Vitamin B6 Vitamin D Vitamin E derivatives Wogonin (5,7-dihydroxy-8-methoxyflavone) Yakuchinone A and B Islam et al., 1998 Suzuki & Packer, 1993 Staal et al., 1993; Suzuki & Packer, 1993 Staal et al., 1993; Son et al., 2004a Yanaka et al., 2005 Cohen-Lahav et al., 2006 Suzuki & Packer, 1993 Lee et al., 2003b; Piao et al., 2004 Chun et al., 2002 23
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