Paper Info
Title
Towards the understanding of the activity of G9a inhibitors: an activity landscape and molecular modeling approach.
Abstract
In this work, we analyze the structure–activity relationships (SAR) of epigenetic inhibitors (lysine mimetics) against lysine methyltransferase (G9a or EHMT2) using a combined activity landscape, molecular docking and molecular dynamics approach. The study was based on a set of 251 G9a inhibitors with reported experimental activity. The activity landscape analysis rapidly led to the identification of activity cliffs, scaffolds hops and other active an inactive molecules with distinct SAR. Structure-based analysis of activity cliffs, scaffold hops and other selected active and inactive G9a inhibitors by means of docking followed by molecular dynamics simulations led to the identification of interactions with key residues involved in activity against G9a, for instance with ASP 1083, LEU 1086, ASP 1088, TYR 1154 and PHE 1158. The outcome of this work is expected to further advance the development of G9a inhibitors.
Year
DOI
Venue
2020
10.1007/s10822-020-00298-x
Journal of Computer-Aided Molecular Design
Keywords
DocType
Volume
Activity cliffs, Drug discovery, EHMT2, Epi-pharmacology, Scaffold hops, Structure–activity relationships
Journal
34
Issue
ISSN
Citations 
6
0920-654X
0
PageRank 
References 
Authors
0.34
0
4
Name
Order
Citations
PageRank
Edgar López-López100.34
Obdulia Rabal21628.61
Julen Oyarzabal3604.85
José L Medina-Franco400.34