* 100102 computer-aided drug design CADD CADD 1-2 2 11-12 CADD - 1 3 3-4 - 13 14-15 1 CADD 5 - QSAR 2005 FDA 16-17 6 7 8 9-10 computer-aided drug design 2013-11-25 81173522 201310026069 2011ZX09401-028 * 1 Tel 010 84738620 E-mail collean_zhang@ 163. com Fig. 1 Virtual screening strategy for multi-target drug 1951
1. 1 2-20 -1-2 Phaedra 21 γ peroxisome proliferator activated receptor γ PPAR-γ 3 4 200 I angiotensin-converting enzyme ACE A hydroxymethylglutaryl coenzyme A receptor HMGR 3 18 51 AutoDock LibDock 5 β2 H1 5 4 A α1 22 C A B 2 2 2 2 1. 2 2 1 1. 4 QSAR 23-24 3 200 Da 3 8 39 72 19 Thomas M Ehrman 25 2 2 4 PDB - 2 2 3 12 1. 3 26-27 I II 1952
I β-amyloid precursor enzyme-1 BACE1 AChE / BACE1 /H3 Leurs R H3 4 29 30 BACEI Ⅱ AChE H3 2 BACE1 AChE 3 31 MTT CAM 2 2 CADD A B. L. C. D. 2 Fig. 2 Pharmacophore design strategy 2. 1 2 ether-à-go-go human ether-à-go-go related gene herg α1a C herg D 2 2 2 2 32 3 CADD 2 28 2 3 2. 2 D2 dopamine D2 receptor DRD2 A 5- serotonin- 2A 5-HT2A B 2 α1a α1a-adrenergic receptors α1a-ar CADD Alzheimer's disease AD AD acetylcholinesterase AChE H3 β- 1953
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29 Leurs R Bakker R A Timmerman H et al. The histamine H3 receptor from gene cloning to H3 receptor drugs J. Nat Rev Drug Disc 2005 4 2 107. 30 Huang W Tang L Shi Y et al. Searching for the multi-targetdirected ligands against Alzheimer's disease discovery of quinoxaline-based hybrid compounds with AChE H3R and BACE1 inhibitory activities J. Bioorg Med Chem 2011 19 23 7158. 31 Wang P She G Yang Y et al. Synthesis and biological evaluation of new ligustrazine derivatives as anti-tumor agents J. Molecules 2012 17 5 4972. 32. D2 /5-HT2A 37. J. 2009 44 3 314. 33. J. Acta Neuropharm 2011 1 4 48. 34 Sheng H Sun H. Synthesis biology and clinical significance of pentacyclic triterpenes a multi-target approach to prevention and treatment of metabolic and vascular diseases J. Nat Prod Rep 2011 28 3 543. 35 Schrattenholz A Soskic V. What does systems biology mean for drug development J. Curr Med Chem 2008 15 15 1520. 36. J. 2010 45 15 1121. J. 2011 36 21 2907. Application of CADD on multi-target drug R&D in natural products QIAO Lian-sheng ZHANG Yan-ling * Research Center of Traditional Chinese Medicine-information Engineering Beijing University of Chinese Medicine Beijing 100102 China Abstract Multi-target drugs can simultaneously adjust multiple links of the disease network. Despite the higher efficacy and lower toxicity caused by single targets multi-target drugs become ideal drugs for treating complicated diseases as well the main direction of drug R & D. By virtue of their structural diversity higher multi-target activity and lower toxicity natural products become an important source for developing multi-target drugs. Computer-aided drug design CADD is a commonly used multi-target drug R&D method which mainly includes virtual screening and pharmacophore design. In this paper the authors made a systematical analysis and discussed the prospects and advantages of various methods for multi-target drug R&D with natural products. Key words multiple target computer-aided drug design natural product pharmacophore docking virtual screening fragment search traditional Chinese medicine doi 10. 4268 /cjcmm20141101 1955