Expanding the range of 'druggable' targets with natural product-based libraries: an academic perspective

被引:124
作者
Bauer, Renato A. [1 ]
Wurst, Jacqueline M. [1 ]
Tan, Derek S. [1 ,2 ,3 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Tri Inst Training Program Chem Biol, New York, NY 10065 USA
[2] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, New York, NY 10065 USA
[3] Mem Sloan Kettering Canc Ctr, Tri Inst Res Program, New York, NY 10065 USA
关键词
DIVERSITY-ORIENTED SYNTHESIS; SPLICING FACTOR SF3B; ATROP-ABYSSOMICIN-C; DRUG DISCOVERY; SCREENING LIBRARIES; SMALL-MOLECULE; PHYSICOCHEMICAL PROPERTIES; CANCER; TRANSCRIPTION; INHIBITOR;
D O I
10.1016/j.cbpa.2010.02.001
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
Existing drugs address a relatively narrow range of biological targets. As a result, libraries of drug-like molecules have proven ineffective against a variety of challenging targets, such as protein-protein interactions, nucleic acid complexes, and antibacterial modalities. In contrast, natural products are known to be effective at modulating such targets, and new libraries are being developed based on underrepresented scaffolds and regions of chemical space associated with natural products. This has led to several recent successes in identifying new chemical probes that address these challenging targets.
引用
收藏
页码:308 / 314
页数:7
相关论文
共 51 条
[1]   Small molecule modulators of transcription [J].
Arndt, Hans-Dieter .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2006, 45 (28) :4552-4560
[2]   Inhibition of transcription factors with small organic molecules [J].
Berg, Thorsten .
CURRENT OPINION IN CHEMICAL BIOLOGY, 2008, 12 (04) :464-471
[3]   Abyssomicin C -: A polycyclic antibiotic from a marine Verrucosispora strain as an inhibitor of the p-aminobenzoic acid/tetrahydrofolate biosynthesis pathway [J].
Bister, B ;
Bischoff, D ;
Ströbele, M ;
Riedlinger, J ;
Reicke, A ;
Wolter, F ;
Bull, AT ;
Zähner, H ;
Fiedler, HP ;
Süssmuth, RD .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2004, 43 (19) :2574-2576
[4]  
Bohacek RS, 1996, MED RES REV, V16, P3, DOI 10.1002/(SICI)1098-1128(199601)16:1<3::AID-MED1>3.0.CO
[5]  
2-6
[6]   Mimicking the BH3 domain to kill cancer cells [J].
Chonghaile, T. Ni ;
Letai, A. .
ONCOGENE, 2008, 27 (Suppl 1) :S149-S157
[7]   Antagonists of protein-protein interactions [J].
Cochran, AG .
CHEMISTRY & BIOLOGY, 2000, 7 (04) :R85-R94
[8]   Chemical space and biology [J].
Dobson, CM .
NATURE, 2004, 432 (7019) :824-828
[9]   Opinion - Carrier-mediated cellular uptake of pharmaceutical drugs: an exception or the rule? [J].
Dobson, Paul D. ;
Kell, Douglas B. .
NATURE REVIEWS DRUG DISCOVERY, 2008, 7 (03) :205-220
[10]   The exploration of macrocycles for drug discovery - an underexploited structural class [J].
Driggers, Edward M. ;
Hale, Stephen P. ;
Lee, Jinbo ;
Terrett, Nicholas K. .
NATURE REVIEWS DRUG DISCOVERY, 2008, 7 (07) :608-624