Wei DG, Jiang XL, Zhou L, Chen J, Chen Z, He C, Yang K, Liu Y, Pei JF, Lai LH*, Discovery of Multitarget Inhibitors by Combining Molecular Docking with Common Pharmacophore Matching. JOURNAL OF MEDICINAL CHEMISTRY, 51 (24), 7882-7888, 2008.

Abstract 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 A(4) 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 microM level. Moreover, one synthetic compound matching the common pharmacophores inhibits LTA4H-h and hnps-PLA2 with IC(50) values of 35 n......