Hit Recycling: Discovery of a Potent Carbonic Anhydrase Inhibitor by in Silico Target Fishing

Mattia Mori, Ylenia Cau, Giulia Vignaroli, Ilaria Laurenzana, Antonella Caivano, Daniela Vullo, Claudiu T. Supuran, Maurizio Botta

Research output: Contribution to journalArticlepeer-review

Abstract

In silico target fishing is an emerging tool in drug discovery, which is mostly used for primary target or off-target prediction and drug repositioning. In this work, we developed an in silico target fishing protocol to identify the primary target of GV2-20, a false-positive hit highlighted in a cell-based screen for 14-3-3 modulators. Although GV2-20 does not bind to 14-3-3 proteins, it showed remarkable antiproliferative effects in CML cells, thus raising interest toward the identification of its primary target. Six potential targets of GV2-20 were prioritized in silico and tested in vitro. Our results show that the molecule is a potent inhibitor of carbonic anhydrase 2 (CA2), thus confirming the predictive capability of our protocol. Most notably, GV2-20 experienced a remarkable selectivity for CA2, CA7, CA9, and CA12, and its scaffold was never explored before as a chemotype for CA inhibition, thus becoming an interesting lead candidate for further development.

Original languageEnglish
Pages (from-to)1964-1969
Number of pages6
JournalACS Chemical Biology
Volume10
Issue number9
DOIs
Publication statusPublished - Sep 18 2015

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Fingerprint

Dive into the research topics of 'Hit Recycling: Discovery of a Potent Carbonic Anhydrase Inhibitor by in Silico Target Fishing'. Together they form a unique fingerprint.

Cite this