Jump to main content
Jump to site search

Issue 17, 2017, Issue in Progress
Previous Article Next Article

Integration of pharmacophore mapping and molecular docking in sequential virtual screening: towards the discovery of novel JAK2 inhibitors

Author affiliations

Abstract

An integrated virtual screening protocol by combining molecular docking and pharmacophore mapping was established to identify novel inhibitors of JAK2 from a commercial compound database. Twelve novel and structurally diverse hits were selected and subjected to in vitro biological tests, and three compounds (A5, A6 and A9) with remarkable JAK2 inhibitory activity were identified. Then, the obtained structures were further used as the template for a subsequent similarity search, leading to the identification of another two promising compounds (B2 and B4). Selectivity profiles of JAK subtype and in vitro anti-cancer activity of the promising compounds were studied, revealing the promising compound B2 was of interest for further study because of its JAK2 selective profile, novelty of skeleton and significantly anti-proliferative effect against cancer cells. Finally, binding patterns of the compounds A5 and B2 were explored to provide a deeper insight for further structural optimization.

Graphical abstract: Integration of pharmacophore mapping and molecular docking in sequential virtual screening: towards the discovery of novel JAK2 inhibitors

Back to tab navigation

Supplementary files

Article information


Submitted
09 Oct 2016
Accepted
24 Jan 2017
First published
07 Feb 2017

This article is Open Access

RSC Adv., 2017,7, 10353-10360
Article type
Paper

Integration of pharmacophore mapping and molecular docking in sequential virtual screening: towards the discovery of novel JAK2 inhibitors

T. Yao, J. Xie, X. Liu, J. Cheng, C. Zhu, J. Zhao and X. Dong, RSC Adv., 2017, 7, 10353
DOI: 10.1039/C6RA24959K

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

Reproduced material should be attributed as follows:

  • For reproduction of material from NJC:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
  • For reproduction of material from PCCP:
    [Original citation] - Published by the PCCP Owner Societies.
  • For reproduction of material from PPS:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
  • For reproduction of material from all other RSC journals:
    [Original citation] - Published by The Royal Society of Chemistry.

Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.


Social activity

Search articles by author

Spotlight

Advertisements