NF-κB inhibitors for the treatment of inflammatory diseases and cancer

被引:129
作者
Calzado, Marco A. [1 ]
Bacher, Susanne [1 ]
Schmitz, M. Lienhard [1 ]
机构
[1] Univ Giessen, Inst Biochem, Fac Med, D-35392 Giessen, Germany
关键词
inflammation; cancer; NF-kappa B; inhibitor; I kappa B; IKK; transcription factor;
D O I
10.2174/092986707779941113
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The NF-kappa B/Rel signaling system is a paradigm for gene activation in response to inflammatory and menacing stimuli. Given the growing body of evidence showing an important involvement of NF-kappa B for the onset of autoimmune diseases and different types of cancer, NF-kappa B is an important drug target for the adjuvant therapy of these diseases. Great efforts have been made for the development of highly specific NF-kappa B inhibitors, some of them being currently tested in phase II clinical trials. Here we discuss recent progress in the identification of druggable components of the NF-kappa B signaling system and the development and potential use of novel NF-kappa B inhibitors.
引用
收藏
页码:367 / 376
页数:10
相关论文
共 102 条
[21]   A fully dissociated compound of plant origin for inflammatory gene repression [J].
De Bosscher, K ;
Vanden Berghe, W ;
Beck, IME ;
Van Molle, W ;
Hennuyer, N ;
Hapgood, J ;
Libert, C ;
Staels, B ;
Louw, A ;
Haegeman, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (44) :15827-15832
[22]   Absence of tumor necrosis factor rescues RelA-deficient mice from embryonic lethality [J].
Doi, TS ;
Marino, MW ;
Takahashi, T ;
Yoshida, T ;
Sakakura, T ;
Old, LJ ;
Obata, Y .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (06) :2994-2999
[23]   Activation of IKK by TNFα requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO [J].
Ea, CK ;
Deng, L ;
Xia, ZP ;
Pineda, G ;
Chen, ZJJ .
MOLECULAR CELL, 2006, 22 (02) :245-257
[24]   NF-κB:: Holy grail for rheumatoid arthritis? [J].
Firestein, GS .
ARTHRITIS AND RHEUMATISM, 2004, 50 (08) :2381-2386
[25]   A role for NF-κB subunits p50 and p65 in the inhibition of lipopolysaccharide-induced shock [J].
Gadjeva, M ;
Tomczak, MF ;
Zhang, M ;
Wang, YY ;
Dull, K ;
Rogers, AB ;
Erdman, SE ;
Fox, JG ;
Carroll, M ;
Horwitz, BH .
JOURNAL OF IMMUNOLOGY, 2004, 173 (09) :5786-5793
[26]   Missing pieces in the NF-κB puzzle [J].
Ghosh, S ;
Karin, M .
CELL, 2002, 109 :S81-S96
[27]   Malignant transformation of primary chicken spleen cells by human transcription factor c-Rel [J].
Gilmore, TD ;
Cormier, C ;
Jean-Jacques, J ;
Gapuzan, ME .
ONCOGENE, 2001, 20 (48) :7098-7103
[28]   IKKβ links inflammation and tumorigenesis in a mouse model of colitis-associated cancer [J].
Greten, FR ;
Eckmann, L ;
Greten, TF ;
Park, JM ;
Li, ZW ;
Egan, LJ ;
Kagnoff, MF ;
Karin, M .
CELL, 2004, 118 (03) :285-296
[29]   Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways [J].
Grimm, Dirk ;
Streetz, Konrad L. ;
Jopling, Catherine L. ;
Storm, Theresa A. ;
Pandey, Kusum ;
Davis, Corrine R. ;
Marion, Patricia ;
Salazar, Felix ;
Kay, Mark A. .
NATURE, 2006, 441 (7092) :537-541
[30]  
Guttridge DC, 1999, MOL CELL BIOL, V19, P5785