Structure-based screening and optimization of cytisine derivatives as inhibitors of the menin-MLL interaction

Chem Commun (Camb). 2016 Apr 30;52(34):5788-91. doi: 10.1039/c6cc01079b. Epub 2016 Mar 23.

Abstract

The natural product-like compound 1 was identified as a direct inhibitor of the menin-MLL interaction by in silico screening. Structure-based optimization furnished analogue 1a, which showed significantly higher potency than both the lead structure 1 and the reference compound MI-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemistry*
  • Alkaloids / pharmacology
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Azocines / chemistry
  • Azocines / pharmacology
  • Hep G2 Cells
  • Histone-Lysine N-Methyltransferase / antagonists & inhibitors*
  • Humans
  • Models, Molecular
  • Myeloid-Lymphoid Leukemia Protein / antagonists & inhibitors*
  • Protein Binding
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Quinolizines / chemistry
  • Quinolizines / pharmacology
  • Structure-Activity Relationship

Substances

  • Alkaloids
  • Antineoplastic Agents
  • Azocines
  • KMT2A protein, human
  • MEN1 protein, human
  • Proto-Oncogene Proteins
  • Quinolizines
  • Myeloid-Lymphoid Leukemia Protein
  • cytisine
  • Histone-Lysine N-Methyltransferase