Exploration of potential ligands against cancer-causing transcription factor E2F3.

Abstract

The transcription factor-based therapeutic approaches are the mainstay of current anticancer drug design options to develop highly selective agents with novel modes of action. In this paper, a homology model of DNA-binding domain of transcription factor E2F3 was generated according to X-ray structure of E2F4. As a first step of our proposed project aspired towards exploration of highly selective potential E2F3 ligands, we performed structure-based virtual screening of ZINC 3D chemical database by using Dock Blaster server. Then 31 compounds, selected by filtration step, were docked against the prominent DNA binding site residues of E2F3 model. Two of them have shown a promising interaction with respect to binding poses. The aim is to propose new active ligands against neoplasias characterized by overexpression of E2F3 transcription factor.

• Authors: Muzammal Hussain, Aqeel Javeed, Muhammad Ashraf, Samerene Siddique, Amjad Riaz, Muhammad Mahmood Mukhtar
• Journal: Pakistan journal of pharmaceutical sciences (Pak J Pharm Sci) Vol. 25 Issue 4 Pg. 793-801 (Oct 2012) ISSN: 1011-601X [Print] Pakistan
• PMID: 23009996 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• E2F3 Transcription Factor
• E2F3 protein, human
• Ligands
• DNA

Topics

• Amino Acid Sequence
• Antineoplastic Agents (chemistry, pharmacology)
• Binding Sites
• Computer-Aided Design
• Crystallography, X-Ray
• DNA (chemistry)
• Databases, Chemical
• Drug Design
• E2F3 Transcription Factor (antagonists & inhibitors, chemistry)
• Humans
• Ligands
• Models, Molecular
• Molecular Sequence Data
• Molecular Structure
• Protein Conformation
• Structure-Activity Relationship