An Isoquinolinium Derivative Selectively Inhibits MAPK Spc1 of the Stress-Activated MAPK Cascade of Schizosaccharomyces pombe

Hyun Jun Kim, Jeong Eun Park, Sangwook Jin, Jung Ho Kim, Kiwon Song

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

We have extended the search for selective inhibitors of the kinases of MAPK cascades by screening a derivative library of one of the isoquinoline rings of the protoberberine backbone. HWY 5069 inhibited the proliferation of wild-type and all mutants of Schizosaccharomyces pombe examined, except spc1Δ, at a minimal inhibitory concentration (MIC) of 3.76 μM. HWY 5069 also completely inhibited Spc1 kinase activity in vitro with an IC50 of 16.4 μM as a competitive inhibitor of substrate binding. It was highly selective for Spc1 and did not affect the activity of other kinases in the MAPK cascades of fission yeast and mammals, including functional homologs of Spc1.

Original languageEnglish
Pages (from-to)881-889
Number of pages9
JournalChemistry and Biology
Volume13
Issue number8
DOIs
Publication statusPublished - 2006 Aug 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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