Small-molecule inhibitors of protein-protein interactions: Progressing towards the dream

被引：1327
作者：
Arkin, MR [1 ]
Wells, JA [1 ]
机构：
[1] Sunesis Pharmaceut, San Francisco, CA 94080 USA
来源：
NATURE REVIEWS DRUG DISCOVERY | 2004年 / 3卷 / 04期
关键词：
D O I：
10.1038/nrd1343
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
Protein-protein interactions have a key role in most biological processes, and offer attractive opportunities for therapeutic intervention. Developing small molecules that modulate protein-protein interactions is difficult, owing to issues such as the lack of well-defined binding pockets. Nevertheless, there has been important progress in this endeavour in recent years. Here, we use illustrative examples to discuss general strategies for addressing the challenges inherent in the discovery and characterization of small-molecule inhibitors of protein-protein interactions.
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页码：301 / 317
页数：17
相关论文
共 179 条
[51]   Structure-activity studies of a series of dipyrazolo[3,4-b:3′,4′-d]pyridin-3-ones binding to the immune regulatory protein B7.1 [J].
Green, NJ ;
Xiang, J ;
Chen, J ;
Chen, LR ;
Davies, AM ;
Erbe, D ;
Tam, S ;
Tobin, JF .
BIOORGANIC & MEDICINAL CHEMISTRY, 2003, 11 (13) :2991-3013
[52]   BCL-2 family members and the mitochondria in apoptosis [J].
Gross, A ;
McDonnell, JM ;
Korsmeyer, SJ .
GENES & DEVELOPMENT, 1999, 13 (15) :1899-1911
[53]   Deletion of exon 6 of the neuronal nitric oxide synthase gene in mice results in hypogonadism and infertility [J].
Gyurko, R ;
Leupen, S ;
Huang, PL .
ENDOCRINOLOGY, 2002, 143 (07) :2767-2774
[54]   NMR-based screening in drug discovery [J].
Hajduk, PJ ;
Meadows, RP ;
Fesik, SW .
QUARTERLY REVIEWS OF BIOPHYSICS, 1999, 32 (03) :211-240
[55]   One-dimensional relaxation- and diffusion-edited NMR methods for screening compounds that bind to macromolecules [J].
Hajduk, PJ ;
Olejniczak, ET ;
Fesik, SW .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1997, 119 (50) :12257-12261
[56]   High-throughput nuclear magnetic resonance-based screening [J].
Hajduk, PJ ;
Gerfin, T ;
Boehlen, JM ;
Häberli, M ;
Marek, D ;
Fesik, SW .
JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (13) :2315-2317
[57]   Design of adenosine kinase inhibitors from the NMR-based screening of fragments [J].
Hajduk, PJ ;
Gomtsyan, A ;
Didomenico, S ;
Cowart, M ;
Bayburt, EK ;
Solomon, L ;
Severin, J ;
Smith, R ;
Walter, K ;
Holzman, TF ;
Stewart, A ;
McGaraughty, S ;
Jarvis, MF ;
Kowaluk, EA ;
Fesik, SW .
JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (25) :4781-4786
[58]   Molecular complexity and its impact on the probability of finding leads for drug discovery [J].
Hann, MM ;
Leach, AR ;
Harper, G .
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, 2001, 41 (03) :856-864
[59]   CD28-MEDIATED SIGNALING CO-STIMULATES MURINE T-CELLS AND PREVENTS INDUCTION OF ANERGY IN T-CELL CLONES [J].
HARDING, FA ;
MCARTHUR, JG ;
GROSS, JA ;
RAULET, DH ;
ALLISON, JP .
NATURE, 1992, 356 (6370) :607-609
[60]  
Hoekstra WJ, 1998, CURR MED CHEM, V5, P195
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