|
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 |
| Molecule | ||
| 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
| Point of Inhibition | ||
| 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 |