Discovery of multitarget inhibitors by combining molecular docking with common pharmacophore matching

Dengguo Wei, Xiaolu Jiang, Lu Zhou, Jing Chen, Zheng Chen, Chong He, Kun Yang, Ying Liu, Jianfeng Pei, Luhua Lai

Research output: Contribution to journalArticlepeer-review

117 Scopus citations


Multitarget drugs have been to be found effective in controlling complex diseases. However, how to design multitarget drugs presents a great challenge. We have developed a computer-assisted strategy to screen for multitarget inhibitors using a combination of molecular docking and common pharmacophore matching. This strategy was successfully applied to screen for dual-target inhibitors against both the human leukotriene A4 hydrolase (LTA4H-h) and the human nonpancreatic secretory phospholipase A2 (hnps-PLA2). Three compounds screened from the chemical database MDL Available Chemical Directory were found to inhibit these two enzymes at the 10 μM level. Moreover, one synthetic compound matching the common pharmacophores inhibits LTA4H-h and hnps-PLA2 with IC50 values of 35 nM and 7.3 μM, respectively. The common pharmacophore model can also be used to search small molecule databases or collections of existing inhibitors, as well as to guide combinatorial library design to search for ideal multitarget inhibitors.

Original languageEnglish (US)
Pages (from-to)7882-7888
Number of pages7
JournalJournal of medicinal chemistry
Issue number24
StatePublished - Dec 25 2008
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery


Dive into the research topics of 'Discovery of multitarget inhibitors by combining molecular docking with common pharmacophore matching'. Together they form a unique fingerprint.

Cite this