title: Spongiacidin C, a pyrrole alkaloid from the marine sponge Stylissa massa, functions as a USP7 inhibitor.
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.
authors.affiliation: Department of Natural Medicines, Graduate School of Pharmaceutical Sciences, Kumamoto University, Oe-honmachi 5-1, Kumamoto 862-0973, Japan.
authors.forename: Michitaka
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Mitsue
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Kodrasov
authors.forename: Henki
authors.initials: H
authors.lastname: Rotinsulu
authors.forename: Fitje
authors.initials: F
authors.lastname: Losung
authors.forename: Remy E P
authors.initials: RE
authors.lastname: Mangindaan
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: de Voogd
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Yokosawa
authors.forename: Benjamin
authors.initials: B
authors.lastname: Nicholson
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tsukamoto
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry*; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D043222:Ubiquitin Thiolesterase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000076084:Ubiquitin-Specific Peptidase 7
chemical_list: D011480:Protease Inhibitors; D011758:Pyrroles; C585543:spongiacidin C; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7