Rational Design and Synthesis of HSF1-PROTACs for Anticancer Drug Development

Molecules. 2022 Mar 2;27(5):1655. doi: 10.3390/molecules27051655.

Abstract

PROTACs employ the proteosome-mediated proteolysis via E3 ligase and recruit the natural protein degradation machinery to selectively degrade the cancerous proteins. Herein, we have designed and synthesized heterobifunctional small molecules that consist of different linkers tethering KRIBB11, a HSF1 inhibitor, with pomalidomide, a commonly used E3 ligase ligand for anticancer drug development.

Keywords: HSF1; KRIBB11; PROTAC; anticancer drug development; thalidomide.

MeSH terms

  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Drug Development*
  • Proteolysis
  • Ubiquitin-Protein Ligases

Substances

  • Antineoplastic Agents
  • Ubiquitin-Protein Ligases
  • pomalidomide