REAGENTS
Inhibitors of Rel/NF-kB
The following tables list compounds that have been reported in the 

literature to inhibit NF-kB or activation of the pathway
  • Anti-oxidants that have been shown to inhibit activation of NF-kB
  • Proteasome and proteases inhibitors that inhibit Rel/NF-kB
  • IkBa phosphorylation and/or degradation inhibitors
  • Miscellaneous inhibitors of NF-kB

    • Table 1 Anti-oxidants that have been shown to inhibit activation of NF-kB
     
    Molecule
    Reference
    a-Lipoic acid Sen et al, 1998; Suzuki et al, 1992
    a-tocopherol Islam et al, 1998
    Aged garlic extract (allicin) Ide & Lau, 2001; Lang et al, 2004; Hasan et al, 2007
     2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)                 Yun et al, 2005
        N-acetyldopamine dimers (from P. cicadae)            Xu et al, 2006
                           Allopurinol      Gomez-Cabrera et al, 2006
                         Anetholdithiolthione              Sen et al, 1996
                              Apocynin            Barbieri et al, 2004
                              Apple juice/extracts    Shi & Jiang, 2002; Davis et al, 2006
                              Aretemsia p7F (5,6,3',5'-tetramethoxy 7,4'-hydroxyflavone)            Lee et al, 2004
                              Astaxanthin            Lee et al, 2003
                              Autumn olive extracts           Wang et al, 2007
    Avenanthramides (from oats) Guo et al, 2007; Sur et al, 2008
                              Benidipine   Matsubara & Hazegawa, 2004
                             bis-eugenol          Murakami et al, 2003
    Bruguiera gymnorrhiza compounds Homhual et al, 2006
    Butylated hydroxyanisole (BHA) Israël et al, 1992; Schulze-Osthoff et al, 1993
    Cepharanthine Okamoto et al, 1994; Tamatani et al, 2007
    Caffeic Acid Phenethyl Ester (3,4-dihydroxycinnamic acid, CAPE) Natarajan et al, 1996; Nagasaka et al, 2007
                                Carnosol        Lo et al, 2002; Huang et al, 2005
                                beta-Carotene            Bai et al, 2005; Guruvayoorappan & Kuttan, 2007
                            Carvedilol Yang et al, 2003
                         Catechol Derivatives       Suzuki & Packer, 1994; Zheng et al, 2008
                   Centaurea L (Asteraceae) extracts Karamenderes et al, 2007
                   Chalcone Liu et al, 2007
                          Chlorogenic acid Feng et al, 2005
                         5-chloroacetyl-2-amnio-1,3-selenazoles Nam et al, 2008
                          Cholestin Lin et al, 2007
                          Chroman-2-carboxylic acid N-substituted phenylamides Kwak et al, 2008
    Cocoa polyphenols Lee et al, 2006
     Coffee extract (3-methyl-1,2-cyclopentanedione)    Chung et al, 2007
                Crataegus pinnatifida polyphenols     Kao et al, 2007
                Curcumin (Diferulolylmethane); dimethoxycurcumin; EF24 analog      Singh & Aggarwal, 1995; Pae et al, 2008; Kasinski et al, 2008
        Dehydroepiandrosterone (DHEA) and     DHEA-sulfate (DHEAS)          Iwasaki et al, 2004; Liu et al, 2005
    Dibenzylbutyrolactone lignans Cho et al, 2002
    Diethyldithiocarbamate (DDC) Schreck et al, 1992
    Diferoxamine Sappey et al, 1995; Schreck et al, 1992
                         Dihydroisoeugenol; isoeugenol        Murakami et al, 1995; Park et al, 2007
                         Dihydrolipoic Acid       Suzuki et al, 1992, 1995
    Dilazep + fenofibric acid Sonoki et al, 2003; Yang et al, 2005
    Dimethyldithiocarbamates (DMDTC) Pyatt et al, 1998
    Dimethylsulfoxide (DMSO) Kelly et al, 1994
    Disulfiram Schreck et al, 1992
                                Ebselen           Schreck et al, 1992
    Edaravone Kokura et al, 2005; Arii et al, 2007; Yoshida et al, 2007
    EPC-K1 (phosphodiester compound of vitamin E and vitamin C) Hirano et al, 1998
    Epigallocatechin-3-gallate (EGCG; green tea polyphenols) Lin & Lin, 1997; Yang et al,1998; Hou et al, 2007
                           Ergothioneine          Rahman et al, 2003
          Ethyl Pyruvate (Glutathione depletion)            Song et al, 2004; Tsung et al, 2005; Jimenez-Lopez et al, 2008
    Ethylene Glycol Tetraacetic Acid (EGTA) Janssen et al, 1999
                                Exercise Goto et al, 2007
                               Fisetin Park et al, 2006; Sung et al, 2007
                 Flavonoids (Crataegus; Boerhaavia diffusa root; xanthohumol; Eupatorium arnottianum; genistein; kaempferol; quercetin, daidzein; flavone; isorhamnetin; naringenin; pelargonidin; finestin; Sophora flavescens; Seabuckthorn fruit berry) Zhang et al, 2004; Chen et al, 2004; Pandey et al, 2005; Albini et al, 2005; Colgate et al, 2006; Clavin et al, 2007; Hamalainen et al, 2008; Zheng et al, 2008; Jung et al, 2008; Mishra et al, 2008
                               Folic acid Au-Yeung et al, 2006
    Gamma-glutamylcysteine synthetase (gamma-GCS) Manna et al, 1999
           Ganoderma lucidum polysaccharides           Zhang et al, 2003; Ho et al, 2007
           Garcinol (from extract of Garcinia indica fruit rind)     Liao et al, 2004
                      Ginkgo biloba extract       Chen et al, 2003
                        Glutathione Cho et al, 1998; Schreck et al, 1992; Wang et al, 2007
                               Guaiacol (2-methoxyphenol)  Murakami et al, 2007
                               Hematein       Choi et al, 2003
                             Hinokitiol     Byeon et al, 2008
                               HMCO5 herbal extract     Kim et al, 2007
                               Hydroquinone            Pyatt et al, 1998; Yang et al, 2006
                        23-hydroxyursolic acid     Shin et al, 2004
    IRFI 042 (Vitamin E-like compound) Altavilla et al, 2001
                               Iron tetrakis    Kang et al, 2001
                                Isosteviol Xu et al, 2008
                                Isovitexin   Lin et al, 2005
    Isoliquiritigenin  Kumar et al, 2007; Kim et al, 2008; Kim et al, 2008
    Kallistatin  Shen et al, 2008
    Kangen-karyu extract Satoh et al, 2005; Yokozawa et al, 2007
    L-cysteine Mihm et al, 1991
    Lacidipine Cominacini et al, 1997
                               Lazaroids       Marubayashi et al, 2002
                               Ligonberries         Wang et al, 2005
                               Lupeol       Saleem et al, 2004; Lee et al, 2007
                               Magnolol Chen et al, 2002; Ou et al, 2006; Kim et al, 2007
                               Maltol Yang et al, 2006
    Manganese superoxide dismutase (Mn-SOD) Manna et al, 1998
    Extract of the stem bark of Mangifera indica L. Leiro et al, 2004; Garrido et al, 2005
                               Melatonin Gilad et al, 1998; Mohan et al, 1995; Li et al, 2005
    21 (alpha, beta)-methylmelianodiol  Zhou et al, 2007
    Mulberry anthocyanins Chen et al, 2006
    N-acetyl-L-cysteine (NAC) Schreck et al, 1991
    Nacyselyn (NAL) Antonicelli et al, 2002
    Nordihydroguaiaritic acid (NDGA) Brennan & O'Neill, 1998; Israël et al,1992; Schulze-Osthoff et al, 1993; Staal et al, 1993
                              Ochnaflavone Suh et al, 2006
                              Onion extract (2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyranone) Ban et al, 2007; Tang et al, 2008
    Orthophenanthroline Schreck et al, 1992
    N-(3-oxo-dodecanoyl) homoserine lactone Kravchenko et al, 2008
    Paricalcitol  Tan et al, 2008
    Phenolic antioxidants (Hydroquinone and tert-butyl hydroquinone) Ma et al, 2003
    alkenylphenols from Piper obliquum Valdivia et al, 2008
    alpha-phenyl-n-tert-butyl-nitrone (PBN)  Kotake et al, 1998;Lin et al, 2006
    Phenylarsine oxide (PAO, tyrosine phosphatase inhibitor) Arbault et al, 1998
                     Phyllanthus urinaria   Chularojmontri et al, 2005; Shen et al, 2007
                     Phytosteryl ferulates (rice bran)      Islam et al, 2008
                     Piper longum Linn. extract      Singh et al, 2007
                     Pitavastatin     Tounai et al, 2007; Wang & Kitajima, 2007
                     Prodelphinidin B2 3, 3' di-O-gallate  Hou et al, 2007
                     Pterostilbene Cichocki et al, 2008
    Pyrrolinedithiocarbamate (PDTC) Schreck et al, 1992
    Quercetin Musonda & Chipman, 1998; Shih et al, 2004; Garcia-Mediavilla et al, 2006; Ruiz et al, 2007; Min et al, 2007; Kim et al, 2007
    Red orange extract Cimini et al, 2008
    Red wine Blanco-Colio et al, 2000; Cui & He, 2004
                       Ref-1 (redox factor 1)     Ozaki et al, 2002
                Rg(3), a ginseng derivative     Keum et al, 2003
                               Rotenone Schulze-Osthoff et al, 1993
                            Roxithromycin Ueno et al, 2005; Ou et al, 2008
                                   Rutin Kyung et al, 2008
    S-allyl-cysteine (SAC, garlic compound) Geng et al, 1997
              Salogaviolide (Centaurea ainetensis)        Ghantous et al, 2008
                              Sauchinone               Lee et al, 2003;           Hwang et al, 2003
                              Silybin            Gazak et al, 2007
                              Spironolactone             Han et al, 2006
                        Strawberry extracts              Wang et al, 2005
                              Taxifolin             Wang et al, 2005
                              Tempol         Cuzzocrea et al, 2004
    Tepoxaline (5-(4-chlorophenyl)-N-hydroxy-(4-methoxyphenyl) -N-methyl-1H-pyrazole-3-propanamide) Kazmi et al, 1995; Ritchie et al, 1995
    Thio avarol derivatives Amigo et al, 2007; Amigo et al, 2008
    Thymoquinone El Gazzar et al, 2007;l Sethi et al, 2008
    Tocotrienol (palm oil) Wu et al, 2008
    Tomato peel polysaccharide De Stefano et al, 2007
    UDN glycoprotein (Ulmus davidiana Nakai) Lee & Lim, 2007
    Vaccinium stamineum (deerberry) extract Wang et al, 2007
    Vanillin (2-hydroxy-3-methoxybenzaldehyde) Murakami et al, 2007
    Vitamin C Staal et al, 1993; Son et al, 2004
                               Vitamin B6           Yanaka et al, 2005
    Vitamin E and derivatives Suzuki & Packer, 1993; Ekstrand-Hammarstrom et al, 2007; Glauert, 2007
    a-torphryl succinate Staal et al, 1993; Suzuki & Packer, 1993
    a-torphryl acetate Suzuki & Packer, 1993
    PMC (2,2,5,7,8-pentamethyl-6-hydroxychromane) Suzuki & Packer, 1993
    Yakuchinone A and B Chun et al, 2002


     

    Table 2a Proteasome and proteases inhibitors that inhibit Rel/NF-kB
    Molecule References
    Proteasome inhibitors
                             Peptide Aldehydes: Palombella et al, 1994; Grisham et al, 1999; Jobin et al, 1998
    ALLnL
    (N-acetyl-leucinyl-leucynil-norleucynal, MG101)
          LLM (N-acetyl-leucinyl-leucynil-methional)
          Z-LLnV 
          (carbobenzoxyl-leucinyl-leucynil-norvalinal,MG115)
          Z-LLL 
          (carbobenzoxyl-leucinyl-leucynil-leucynal, MG132)
    Lactacystine, beta-lactone Fenteany & Schreiber, 1998; Grisham et al, 1999
    Boronic Acid Peptide Grisham et al, 1999; Iqbal et al, 1995
    Dithiocarbamate complexes with metals Cvek & Dvorak, 2007
    CEP-18770 Piva et al, 2007
    Ubiquitin Ligase Inhibitors Yaron et al, 1997
    PS-341 (Bortezomib) Adams, 2004
    Salinosporamide A (1, NPI-0052)  Macherla et al, 2005; Ahn et al, 2007
    Cyclosporin A Frantz et al, 1994; Kunz et al, 1995; Marienfeld et al, 1997; McCaffrey et al, 1994; Meyer et al, 1997; Wechsler et al, 1994
    FK506 (Tacrolimus) Okamoto et al, 1994; Venkataraman et al, 1995
    Deoxyspergualin Tepper et al, 1995
                              Disulfiram            Lovborg et al, 2005
                              PT-110          Momose et al, 2007
     

    Protease inhibitors
    APNE (N-acetyl-DL-phenylalanine-b-naphthylester) Higuchi et al, 1995
    BTEE (N-benzoyl L-tyrosine-ethylester) Rossi et al, 1998
    DCIC (3,4-dichloroisocoumarin) D'Acquisto et al, 1998
    DFP (diisopropyl fluorophosphate)
    TPCK (N-a-tosyl-L-phenylalanine chloromethyl ketone)
    TLCK (N-a-tosyl-L-lysine chloromethyl ketone)


     

    Table 2b IkBa phosphorylation and/or degradation inhibitors
    Molecule
    		 Point of Inhibition
    References
    Desloratadine; diphenhydramine Histamine H1 receptor Wu et al, 2004; Scadding, 2005; Roumestan et al, 2008
    Bikunin LPS receptor agonists Kobayashi, 2006; Kanayama et al, 2007
    Ron Tyrosine kinase receptor Suppresses TNF production Lentsch et al, 2007
    TAK-242 TLR4 intracellular domain Kawamoto et al, 2008
    Salmeterol, fluticasone propionate beta2 agonists Baouz et al, 2005
    CPU0213 Endothelin receptor antagonist He et al, 2006
    Doxazosin alpha1-adrenergic receptor antagonist Hui et al, 2007
    Erbin overexpression NOD2 inhibitor McDonald et al, 2005
    Protein-bound polysaccharide from basidiomycetes LPS-CD14 interaction Asai et al, 2005
    Anti-CD146 antibody AA98 upstream of IKK Bu et al, 2006
    Calagualine (fern derivative) upstream of IKK (TRAF2-NIK) Manna et al, 2003
    NS3/4A (HCV protease) upstream of IKK  Karayiannis, 2005
    golli BG21 (product of myelin basic protein) upstream of IKK (PKC) Feng et al, 2004
    NPM-ALK oncoprotein Traf2 inhibition Horie et al, 2004
    NS5A (Hepatitis C virus) Traf2 inhibition Park et al, 2002
    LY29 and LY30 PI3 Kinase inhibitors Choi et al, 2004
    Shiga toxin (Enterohemorrhagic E coli) PI3 Kinase inhibitor Gobert et al, 2007
    Evodiamine (Evodiae Fructus component) AKT-IKK interaction Takada et al, 2005
    Rituximab (anti-CD20 antibody) up-regulates Raf-1 kinase inhibitor Jazirehi et al, 2005
    Kinase suppressor of ras (KSR2) MEKK3 inhibitor Channavajhala et al, 2005
    Cholecystokinin ocatpeptide (CCK-8) p38 kinase Li et al, 2007
    M2L (Vaccinia virus) ERK2 inhibitor Gedey et al, 2006; Hinthong et al, 2008
    Pefabloc (serine protease inhibitor) upstream of IKK Tando et al, 2002
    Rocaglamides (Aglaia derivatives) upstream of IKK Baumann et al, 2002
    Ymer Binds to Ub-RIP Bohgaki et al, 2007
    Betaine NIK/IKK Go et al, 2004, 2007
    TNAP NIK Hu et al, 2005
    Selected peptides NEMO binding to Ub Wyler et al, 2007
    Desflurane IKK complex formation with TNF-R1 Li et al, 2008
    Geldanamycin IKK complex formation Chen et al, 2002
    Grape seed proanthocyanidins  IKKa activity Mantena & Katiyar, 2006; Sharma et al, 2007; Cheng et al, 2007; Xu et al, 2008
    Laretia acaulis azorellane diterpenoids IKKa activity Borquez et al, 2007
     MC160 (Molluscum contagiosum virus) IKKa activity