Computer-aided drug design and ADMET predictions for identification and evaluation of novel potential farnesyltransferase inhibitors in cancer therapy

J Mol Graph Model. 2010 Feb 26;28(6):513-23. doi: 10.1016/j.jmgm.2009.11.011. Epub 2009 Dec 4.


We have used various computational methodologies including molecular dynamics, density functional theory, virtual screening, ADMET predictions and molecular interaction field studies to design and analyze four novel potential inhibitors of farnesyltransferase (FTase). Evaluation of two proposals regarding their drug potential as well as lead compounds have indicated them as novel promising FTase inhibitors, with theoretically interesting pharmacotherapeutic profiles, when compared to the very active and most cited FTase inhibitors that have activity data reported, which are launched drugs or compounds in clinical tests. One of our two proposals appears to be a more promising drug candidate and FTase inhibitor, but both derivative molecules indicate potentially very good pharmacotherapeutic profiles in comparison with Tipifarnib and Lonafarnib, two reference pharmaceuticals. Two other proposals have been selected with virtual screening approaches and investigated by us, which suggest novel and alternatives scaffolds to design future potential FTase inhibitors. Such compounds can be explored as promising molecules to initiate a research protocol in order to discover novel anticancer drug candidates targeting farnesyltransferase, in the fight against cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer-Aided Design*
  • Crystallography, X-Ray
  • Drug Design*
  • Drug Evaluation, Preclinical / methods*
  • Drug Screening Assays, Antitumor / methods*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Farnesyltranstransferase / antagonists & inhibitors*
  • Molecular Dynamics Simulation*
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Protein Structure, Secondary


  • Enzyme Inhibitors
  • Farnesyltranstransferase