Ensemble docking-based virtual screening yields novel spirocyclic JAK1 inhibitors

Dávid Bajusz, G. Ferenczy, György M. Keserű

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Small molecule inhibition of Janus kinases (JAKs) has been demonstrated as a viable strategy for the treatment of various inflammatory conditions and continues to emerge in cancer-related indications. In this study, a large supplier database was screened to identify novel chemistry starting points for JAK1. The docking-based screening was followed up by testing ten hit compounds experimentally, out of which five have displayed single-digit micromolar and submicromolar IC50 values on JAK1. Thus, the study was concluded with the discovery of five novel JAK inhibitors from a tiny screening deck with a remarkable hitrate of 50%. The results have highlighted spirocyclic pyrrolopyrimidines with submicromolar JAK1 IC50 values and a preference for JAK1 over JAK2 as potential starting points in developing a novel class of JAK1 inhibitors.

Original languageEnglish
Pages (from-to)275-283
Number of pages9
JournalJournal of Molecular Graphics and Modelling
Volume70
DOIs
Publication statusPublished - Nov 1 2016

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Keywords

  • Ensemble docking
  • JAK1
  • Janus kinase
  • Kinase inhibitor
  • Spirocyclic compounds
  • Virtual screening

ASJC Scopus subject areas

  • Spectroscopy
  • Physical and Theoretical Chemistry
  • Computer Graphics and Computer-Aided Design
  • Materials Chemistry

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