Utilizing a structure-based virtual screening approach to discover potential LSD1 inhibitors

J Cancer Res Clin Oncol. 2024 May 15;150(5):253. doi: 10.1007/s00432-024-05784-5.

Abstract

Background: Lysine-specific demethylase 1 (LSD1) is highly expressed in a variety of malignant tumors, rendering it a crucial epigenetic target for anti-tumor therapy. Therefore, the inhibition of LSD1 activity has emerged as a promising innovative therapeutic approach for targeted cancer treatment.

Methods: In our study, we employed innovative structure-based drug design methods to meticulously select compounds from the ZINC15 database. Utilizing virtual docking, we evaluated docking scores and binding modes to identify potential inhibitors. To further validate our findings, we harnessed molecular dynamic simulations and conducted meticulous biochemical experiments to deeply analyze the binding interactions between the protein and compounds.

Results: Our results showcased that ZINC10039815 exhibits an exquisite binding mode with LSD1, fitting perfectly into the active pocket and forming robust interactions with multiple critical residues of the protein.

Conclusions: With its significant inhibitory effect on LSD1 activity, ZINC10039815 emerges as a highly promising candidate for the development of novel LSD1 inhibitors.

Keywords: Docking; Inhibitor; LSD1; Molecular dynamics simulation.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Drug Design
  • Enzyme Inhibitors* / chemistry
  • Enzyme Inhibitors* / pharmacology
  • Histone Demethylases* / antagonists & inhibitors
  • Histone Demethylases* / chemistry
  • Histone Demethylases* / metabolism
  • Humans
  • Molecular Docking Simulation*
  • Molecular Dynamics Simulation
  • Neoplasms / drug therapy
  • Neoplasms / metabolism