Spongiacidin C, a pyrrole alkaloid from the marine sponge Stylissa massa, functions as a USP7 inhibitor

Bioorg Med Chem Lett. 2013 Jul 1;23(13):3884-6. doi: 10.1016/j.bmcl.2013.04.066. Epub 2013 May 3.

Abstract

USP7, a deubiquitylating enzyme hydrolyzing the isopeptide bond at the C-terminus of ubiquitin, is an emerging cancer target. We isolated spongiacidin C from the marine sponge Stylissa massa as the first USP7 inhibitor from a natural source. This compound inhibited USP7 most strongly with an IC50 of 3.8 μM among several USP family members tested.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Porifera / chemistry*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Pyrroles / chemistry
  • Pyrroles / isolation & purification
  • Pyrroles / pharmacology*
  • Structure-Activity Relationship
  • Ubiquitin Thiolesterase / antagonists & inhibitors*
  • Ubiquitin Thiolesterase / metabolism
  • Ubiquitin-Specific Peptidase 7

Substances

  • Protease Inhibitors
  • Pyrroles
  • spongiacidin C
  • USP7 protein, human
  • Ubiquitin Thiolesterase
  • Ubiquitin-Specific Peptidase 7