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

Michitaka Yamaguchi; Mitsue Miyazaki; Matthew P Kodrasov; Henki Rotinsulu; Fitje Losung; Remy E P Mangindaan; Nicole J de Voogd; Hideyoshi Yokosawa; Benjamin Nicholson; Sachiko Tsukamoto

doi:10.1016/j.bmcl.2013.04.066

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.

Authors

Michitaka Yamaguchi¹, Mitsue Miyazaki, Matthew P Kodrasov, Henki Rotinsulu, Fitje Losung, Remy E P Mangindaan, Nicole J de Voogd, Hideyoshi Yokosawa, Benjamin Nicholson, Sachiko Tsukamoto

Affiliation

¹ Department of Natural Medicines, Graduate School of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi 5-1, Kumamoto 862-0973, Japan.

PMID: 23684893
DOI: 10.1016/j.bmcl.2013.04.066

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