Elraglusib Induces Cytotoxicity via Direct Microtubule Destabilization Independently of GSK3 Inhibition

Cancer Res Commun. 2024 Nov 1;4(11):3013-3024. doi: 10.1158/2767-9764.CRC-24-0408.

Abstract

Elraglusib was designed as a GSK3 inhibitor and is currently in clinical trials for several cancers. We show conclusively that the target of elraglusib that leads to cytotoxicity is MTs and not GSK3. This has significant implications for ongoing clinical trials of the compound and will help in understanding off-target side effects, inform future clinical trial design, and facilitate the development of biomarkers to predict response.

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Glycogen Synthase Kinase 3* / antagonists & inhibitors
  • Glycogen Synthase Kinase 3* / metabolism
  • Humans
  • Microtubules* / drug effects
  • Microtubules* / metabolism
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacology

Substances

  • Glycogen Synthase Kinase 3
  • Antineoplastic Agents
  • Protein Kinase Inhibitors