1. Academic Validation
  2. Practical synthesis of a phthalimide-based Cereblon ligand to enable PROTAC development

Practical synthesis of a phthalimide-based Cereblon ligand to enable PROTAC development

  • Bioorg Med Chem Lett. 2016 Nov 1;26(21):5260-5262. doi: 10.1016/j.bmcl.2016.09.048.
Jasmin Lohbeck 1 Aubry K Miller 2
Affiliations

Affiliations

  • 1 Cancer Drug Development Group, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
  • 2 Cancer Drug Development Group, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. Electronic address: aubry.miller@dkfz.de.
Abstract

The use of small molecules to regulate cellular levels of specific proteins is poised to become a powerful technique in the coming years. Critical to the success of any project utilizing such an approach will be the ability to synthesize libraries of candidate small molecules for testing in cellular systems. Herein, we describe a practical synthesis of a phthalimide-based scaffold, which can be easily diversified to make Cereblon-targeting PROTACs. We demonstrate the effectiveness of this approach by synthesizing a 'PROTAC toolbox' of four amines which can be coupled to inhibitors in a straightforward manner.

Keywords

Cereblon; E3 ligase; PROTACs; Thalidomide.

Figures
Products