title: Use of natural products as chemical library for drug discovery and network pharmacology.
abstract: BACKGROUND
  Natural products have been an important source of lead compounds for drug discovery. How to find and evaluate bioactive natural products is critical to the achievement of drug/lead discovery from natural products.
  
  
  METHODS
  We collected 19,7201 natural products structures, reported biological activities and virtual screening results. Principal component analysis was employed to explore the chemical space, and we found that there was a large portion of overlap between natural products and FDA-approved drugs in the chemical space, which indicated that natural products had large quantity of potential lead compounds. We also explored the network properties of natural product-target networks and found that polypharmacology was greatly enriched to those compounds with large degree and high betweenness centrality. In order to make up for a lack of experimental data, high throughput virtual screening was employed. All natural products were docked to 332 target proteins of FDA-approved drugs. The most potential natural products for drug discovery and their indications were predicted based on a docking score-weighted prediction model.
  
  
  CONCLUSIONS
  Analysis of molecular descriptors, distribution in chemical space and biological activities of natural products was conducted in this article. Natural products have vast chemical diversity, good drug-like properties and can interact with multiple cellular target proteins.
authors: Beijing National Laboratory for Molecular Sciences, State Key Lab of Rare Earth Material Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing, PR China.
authors: Jiangyong
authors: J
authors: Gu
authors: Yuanshen
authors: Y
authors: Gui
authors: Lirong
authors: L
authors: Chen
authors: Gu
authors: G
authors: Yuan
authors: Hui-Zhe
authors: HZ
authors: Lu
authors: Xiaojie
authors: X
authors: Xu
mesh_terms: D001688:Biological Products / Q000494:pharmacology*; D019295:Computational Biology; D062313:Databases, Pharmaceutical; D004194:Disease; D017277:Drug Approval; D055808:Drug Discovery / Q000379:methods*; D010600:Pharmacology / Q000379:methods*; D014481:United States; D014486:United States Food and Drug Administration / Q000331:legislation & jurisprudence
chemical_list: D001688:Biological Products
references: Chem Cent J. 2008 Sep 08;2:18
references: 18778471
references: J Chem Inf Comput Sci. 2001 Mar-Apr;41(2):273-7
references: 11277710
references: Drug Discov Today. 2012 May;17(9-10):413-8
references: 22155224
references: J Comput Chem. 2009 Dec;30(16):2785-91
references: 19399780
references: Nutr Cancer. 2007;59(2):152-62
references: 18001209
references: Science. 2009 Sep 18;325(5947):1544-9
references: 19762644
references: J Nat Prod. 2008 Mar;71(3):464-8
references: 18257534
references: J Nat Prod. 2011 Mar 25;74(3):496-511
references: 21138324
references: Arch Pharm Res. 2007 Jul;30(7):820-6
references: 17703732
references: Drug Discov Today. 2012 Jul;17(13-14):718-26
references: 22515962
references: J Chem Inf Comput Sci. 2003 Jan-Feb;43(1):218-27
references: 12546556
references: Nat Prod Rep. 2003 Aug;20(4):382-91
references: 12964834
references: Eur J Med Chem. 2010 Dec;45(12):5646-52
references: 20888084
references: Bioinformatics. 2011 Feb 1;27(3):431-2
references: 21149340
references: Nature. 2012 Jan 25;481(7382):455-6
references: 22281594
references: Am J Physiol Regul Integr Comp Physiol. 2009 Apr;296(4):R1071-7
references: 19211721
references: Nat Biotechnol. 2012 Jan 15;30(2):159-64
references: 22252508
references: J Chem Inf Comput Sci. 2002 May-Jun;42(3):481-9
references: 12086505
references: Mol Inform. 2010 Jan 12;29(1-2):10-4
references: 27463845
references: Nature. 2004 Dec 16;432(7019):824-8
references: 15602547
references: PLoS Comput Biol. 2007 Mar 23;3(3):e55
references: 17381237
references: BMC Bioinformatics. 2006 Apr 21;7:219
references: 16630347
references: Drug Discov Today. 2011 Nov;16(21-22):976-84
references: 21782967
references: J Nat Prod. 2012 Mar 23;75(3):311-35
references: 22316239
references: Curr Opin Chem Biol. 2011 Jun;15(3):350-4
references: 21489856
references: Acta Pharmacol Sin. 2007 Mar;28(3):404-9
references: 17303004
references: Nat Chem Biol. 2008 Nov;4(11):682-90
references: 18936753
references: Chem Biol Drug Des. 2012 Nov;80(5):717-24
references: 22863071
references: J Comb Chem. 2001 May-Jun;3(3):284-9
references: 11350252
references: Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):3-26
references: 11259830
references: Mem Inst Oswaldo Cruz. 2005 Oct;100(6):475-506
references: 16302058
references: Angew Chem Int Ed Engl. 1999 Mar 1;38(5):643-647
references: 29711552
references: Cancer. 2010 Jan 1;116(1):164-76
references: 19894226
references: Eur J Med Chem. 2009 Dec;44(12):5006-11
references: 19782440
references: Nature. 2004 Dec 16;432(7019):855-61
references: 15602551
references: J Clin Pharmacol. 2008 Jun;48(6):763-75
references: 18508951
references: Nucleic Acids Res. 2012 Jan;40(Database issue):D1100-7
references: 21948594
references: Drug Discov Today. 2008 Oct;13(19-20):894-901
references: 18691670
references: AAPS J. 2006 Apr 14;8(2):E239-53
references: 16796374
references: Comput Biol Chem. 2011 Oct 12;35(5):293-7
references: 22000800
references: Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36
references: 21948793
references: J Med Chem. 2009 Apr 9;52(7):1953-62
references: 19265440
references: J Cheminform. 2011 Oct 07;3:33
references: 21982300
references: Curr Med Chem. 2003 Nov;10(21):2327-42
references: 14529345
references: Nature. 2004 Dec 16;432(7019):829-37
references: 15602548
references: Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201
references: 17145705
references: J Comput Chem. 2011 May;32(7):1466-74
references: 21425294
references: Nat Prod Rep. 2008 Oct;25(5):892-904
references: 18820757
references: J Antibiot (Tokyo). 1977 Apr;30(4):275-82
references: 863788
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41
references: 21059682
references: Nat Chem. 2012 Jan 24;4(2):90-8
references: 22270643
references: Nat Biotechnol. 2007 Oct;25(10):1119-26
references: 17921997
references: Nat Prod Rep. 2010 Apr;27(4):489-98
references: 20336234
references: Nat Biotechnol. 2007 Oct;25(10):1110-1
references: 17921993
references: PLoS One. 2011 Mar 22;6(3):e14774
references: 21445339
references: J Med Chem. 2002 May 23;45(11):2213-21
references: 12014959
references: Curr Pharm Des. 2010 May;16(15):1703-17
references: 20222853
references: Nat Rev Drug Discov. 2007 Nov;6(11):881-90
references: 17971784
references: EMBO Rep. 2009 Mar;10(3):194-200
references: 19229284