The Mystery of EVP4593: Perspectives of the Quinazoline-Derived Compound in the Treatment of Huntington's Disease and Other Human Pathologies

Int J Mol Sci. 2022 Dec 11;23(24):15724. doi: 10.3390/ijms232415724.

Abstract

Quinazoline derivatives have various pharmacological activities and are widely used in clinical practice. Here, we reviewed the proposed mechanisms of the physiological activity of the quinazoline derivative EVP4593 and perspectives for its clinical implication. We summarized the accumulated data about EVP4593 and focused on its activities in different models of Huntington's disease (HD), including patient-specific iPSCs-based neurons. To make a deeper insight into its neuroprotective role in HD treatment, we discussed the ability of EVP4593 to modulate calcium signaling and reduce the level of the huntingtin protein. Moreover, we described possible protective effects of EVP4593 in other pathologies, such as oncology, cardiovascular diseases and parasite invasion. We hope that comprehensive analyses of the molecular mechanisms of EVP4593 activity will allow for the expansion of the scope of the EVP4593 application.

Keywords: EVP4593; Huntington’s disease; NF-κB signaling; QNZ; calcium signaling; huntingtin; neurodegeneration; oncology; quinazoline derivatives; store-operated calcium entry.

Publication types

  • Review

MeSH terms

  • Humans
  • Huntingtin Protein / metabolism
  • Huntington Disease* / metabolism
  • Neurons / metabolism
  • Phenyl Ethers / pharmacology
  • Quinazolines / metabolism
  • Quinazolines / pharmacology
  • Quinazolines / therapeutic use

Substances

  • EVP 4593
  • Quinazolines
  • Phenyl Ethers
  • Huntingtin Protein