Design, synthesis and evaluation of benzoisothiazolones as selective inhibitors of PHOSPHO1

Yalda Bravo, Peter Teriete, Raveendra Panickar Dhanya, Russell Dahl, Pooi San Lee, Tina Kiffer-Moreira, Santhi Reddy Ganji, Eduard Sergienko, Layton H. Smith, Colin Farquharson, José Luis Millán, Nicholas D P Cosford*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


We report the discovery and characterization of a series of benzoisothiazolone inhibitors of PHOSPHO1, a newly identified soluble phosphatase implicated in skeletal mineralization and soft tissue ossification abnormalities. High-throughput screening (HTS) of a small molecule library led to the identification of benzoisothiazolones as potent and selective inhibitors of PHOSPHO1. Critical structural requirements for activity were determined, and the compounds were subsequently derivatized and measured for in vitro activity and ADME parameters including metabolic stability and permeability. On the basis of its overall profile the benzoisothiazolone analogue 2q was selected as MLPCN probe ML086.

Original languageEnglish
Pages (from-to)4308-4311
JournalBioorganic & Medicinal Chemistry Letters
Issue number17
Early online date15 Jul 2014
Publication statusPublished - 12 Aug 2014


  • ML086
  • Phosphatase
  • Probe compound
  • Vascular calcification


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