poproteinlipase LPL

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1 * HMG-CoA PPAR-α HMG-CoA PPAR-α PPAR-α PPAR-α 8 - DS Receptor-Ligand Pharmacophore Generation Screen Library N CAI TCMD poproteinlipase LPL TG LDL-C HDL-C HMG-CoA LDL-C HDL-C - 2 HMG-CoA 7 αperoxisome proliferator receptor-alpha PPAR-α li- 8 PDB Protein Data Bank PPAR-α ZX BJGJ * Tel collean_zhang@ 163. com 4839

2 39 24 world traditional medicine patent database WTM PPAR-α HMG-CoA 1 ~ PDB PPAR-α CAI comprehensive appraisal index CAI N A The Binding Database http/ /www. bindingdb. org /bind /index. jsp A% = H a 100% A PPAR-α 269 MDDR MDL Drug Data ReportVersion CAI = N N = H a /H t A /D = H a D H t A A% N N A% N A% Y% = H a 100% H t traditional Chinese medi- 1 PDB PPAR-α cine database TCMD version Table 1 The information of the ligand-receptor complexes of Best PPAR-α from PDB / IC 50 /nmol L - 1 Search 3KDU NKS KDT 7HA K7L NPA MMB P ZNN S FEI CTM VI8 13M DSDiscovery Studio 4. 0Receptor-Ligand Pharmacophore Generation - 2 Screen Library 2. 1 DS Receptor-Ligand Pharmacophore Generation H a H t A Screen D Library Screen A% N A% Library 4840

3 ~ CAI hydrogen bond acceptor A hydrophobic region H 1 1 excluded volumes EV3 N Fig. 1 The first pharmacophore N 3 CAI 1 CAI 3 Table 3 The result of the traditional Chinese medicine from virtual screening CAI Table 2 The CAI top ten pharmacophores based on the structure 32 8 of conjugates No. N CAI H2 A5 H6 A7 H9 2ZNN H2 A3 H4 H5 A6 1K7L A1 H2 A3 H5 H7 1K7L H2 H5 A6 H7 A12 2P A1 H2 A3 H4 H5 1K7L A1 H4 H5 A6 H7 2P A1 H2 H3 A6 H8 H11 3VI H2 H5 A6 H7 A8 2NPA H2 A3 H5 A6 H7 1K7L H1 A5 A7 H9 A10 2ZNN A. H DS

4 Table 4 The result of patent search β PPAR-α 2 PPAR-α 14 NO 16 obovatol A- ACAT ' 4' - cis-9 cis-12- cis-9 2 TG TC

5 J. 1. J Lin S K. Pharmacophore perception development and use in drug 2. J. J. Molecules S J. 13. J J J J. J Yang J. Application of computer-aided drug design to traditional 16. Chinese medicine J. Int J Org Chem J. 7Yang HShen YChen Jet al. Structure-based virtual screening for identification of novel 11β-HSD1 inhibitorsj. Eur J 17. J. Med Chem J. J PDE4B 19. J. J Study on lipid-lowering traditional Chinese medicines based on pharmacophore technology and patent retrieval HUO Xiao-qian 1 HE Yu-su 1 QIAO Lian-sheng 1 SUN Zhi-yi 2 ZHANG Yan-ling 1* 1. Traditional Chinese Medicine Information Engineering Research CenterBeijing University of Chinese MedicineBeijing China 2. Beijing Eastlinden Science & Technology Co. Ltd. Beijing China AbstractThe combined application of statins that inhibit HMG-CoA reductase and fibrates that activate PPAR-α can produce a better lipid-lowering effect than the simple applicationbut with stronger adverse reactions at the same time. In the treatment of hyperlipidemia the combined administration of TCMs and HMG-CoA reductase inhibitor in treating hyperlipidemia shows stable efficacy and less adverse reactionsand provides a new option for the combined application of drugs. In this article the pharmacophore technology was used to search chemical components of TCMs trace their source herbsand determine the potential common TCMs that could activate PPAR-α. Because there is no hyperlipidemia-related medication reference in modern TCM classicsto ensure the high safety and efficacy of all selected TCMswe selected TCMs that are proved to be combined with statins in the World Traditional /Natural Medicine Patent Databaseanalyzed corresponding drugs in pharmacophore results based on thatand finally obtained common TCMs that can be applied in PPAR-α and combined with statins. Specifically the pharmacophore model was based on eight receptor-ligand complexes of PPAR-α. The Receptor-Ligand Pharmacophore Generation module in the DS program was used to build the modeloptimize with the Screen Library moduleand get the best sub-pharmacophorewhich consisted of two hydrogen bond acceptor three hydrophobic groups and 19 excluded volumeswith the identification effectiveness index value N of and the comprehensive evaluation index CAI value of The model was used to screen the TCMD databasehit kinds of chemical components and natural animals and plantsand finally determine 62 TCMs. Through patent retrievalwe found 38 TCMsAfter comparing with the virtual screening resultswe finally got seven TCMs. Key wordslipid-loweringpharmacophorevirtual screeningpatent searchfibratesdrug combination doi /cjcmm