Small molecular weight protein-protein interaction antagonists -: an insurmountable challenge?

被引:99
作者
Doemling, Alexander [1 ,2 ]
机构
[1] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15260 USA
[2] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA
关键词
D O I
10.1016/j.cbpa.2008.04.603
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
Several years ago small molecular weight protein-protein interaction (PPI) antagonists were considered as the Mount Everest in drug discovery and generally regarded as too difficult to be targeted. However, recent industrial and academic research has produced a great number of new antagonists of diverse PPIs. This review structurally analyses small molecular weight PPI antagonists and their particular targets as well as tools to discover such compounds. Besides general discussions there will be a focus on the PPI p53/mdm2.
引用
收藏
页码:281 / 291
页数:11
相关论文
共 45 条
  • [1] Mouse double minute antagonist Nutlin-3a enhances chemotherapy-induced apoptosis in cancer cells with mutant p53 by activating E2F1
    Ambrosini, G.
    Sambol, E. B.
    Carvajal, D.
    Vassilev, L. T.
    Singer, S.
    Schwartz, G. K.
    [J]. ONCOGENE, 2007, 26 (24) : 3473 - 3481
  • [2] ARTS J, 2007, AACR NCIEORTC INT C
  • [3] Small molecule inhibitors of the MDM2-p53 interaction discovered by ensemble-based receptor models
    Bowman, Anna L.
    Nikolovska-Coleska, Zaneta
    Zhong, Haizhen
    Wang, Shaomeng
    Carlson, Heather A.
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2007, 129 (42) : 12809 - 12814
  • [4] Structural details on mdm2-p53 interaction
    Chi, SW
    Lee, SH
    Kim, DH
    Ahn, MJ
    Kim, JS
    Woo, JY
    Torizawa, T
    Kainosho, M
    Han, KH
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (46) : 38795 - 38802
  • [5] A HOT-SPOT OF BINDING-ENERGY IN A HORMONE-RECEPTOR INTERFACE
    CLACKSON, T
    WELLS, JA
    [J]. SCIENCE, 1995, 267 (5196) : 383 - 386
  • [6] Substituted 1,4-benzodiazepine-2,5-diones as α-helix mimetic antagonists of the HDM2-p53 protein-protein interaction
    Cummings, MD
    Schubert, C
    Parks, DJ
    Calvo, RR
    LaFrance, LV
    Lattanze, J
    Milkiewicz, KL
    Lu, TB
    [J]. CHEMICAL BIOLOGY & DRUG DESIGN, 2006, 67 (03) : 201 - 205
  • [7] Monitoring the effects of antagonists on protein-protein interactions with NMR spectroscopy
    D'Silva, L
    Ozdowy, P
    Krajewski, M
    Rothweiler, U
    Singh, M
    Holak, TA
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2005, 127 (38) : 13220 - 13226
  • [8] Updates on p53: modulation of p53 degradation as a therapeutic approach
    Dey, A.
    Verma, C. S.
    Lane, D. P.
    [J]. BRITISH JOURNAL OF CANCER, 2008, 98 (01) : 4 - 8
  • [9] Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction
    Ding, Ke
    Lu, Yipin
    Nikolovska-Coleska, Zaneta
    Wang, Guoping
    Qiu, Su
    Shangary, Sanjeev
    Gao, Wei
    Qin, Dongguang
    Stuckey, Jeanne
    Krajewski, Krzysztof
    Roller, Peter P.
    Wang, Shaomeng
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (12) : 3432 - 3435
  • [10] Mdm4 and Mdm2 cooperate to inhibit p53 activity in proliferating and quiescent cells in vivo
    Francoz, S
    Froment, P
    Bogaerts, S
    De Clercq, S
    Maetens, M
    Doumont, G
    Bellefroid, E
    Marine, JC
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (09) : 3232 - 3237