Selective inhibition of p97 by chlorinated analogues of dehydrocurvularin

Joseph Tillotson, Bharat P. Bashyal, Minjin Kang, Taoda Shi, Fabian De La Cruz, A. A.Leslie Gunatilaka, Eli Chapman

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


The ATPase p97 is a ubiquitin targeted segregase that uses the energy of ATP binding and hydrolysis to extract ubiquitylated substrates from biological membranes, from other proteins, or from protein complexes to carry out myriad tasks in eukaryotes. Increased p97 activity has been linked to a poor prognosis in cancer patients, making p97 an anti-neoplastic target. In the present study, we show that dehydrocurvularin (DHC) and its chlorinated variants are covalent inhibitors of p97, interfering with its ATPase activity. Interestingly, cellular studies revealed both DHC and its monochloro analogue interfere with both the proteasome and p97, whereas its dichloro analogue showed p97 specificity.

Original languageEnglish (US)
Pages (from-to)5918-5921
Number of pages4
JournalOrganic and Biomolecular Chemistry
Issue number25
StatePublished - 2016

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry


Dive into the research topics of 'Selective inhibition of p97 by chlorinated analogues of dehydrocurvularin'. Together they form a unique fingerprint.

Cite this