Identification, synthesis and evaluation of substituted benzofurazans as inhibitors of CREB-mediated gene transcription

Fuchun Xie, Bingbing X. Li, Candice Broussard, Xiangshu Xiao

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Cyclic-AMP response-element binding protein (CREB) is a stimulus-activated transcription factor. Its transcription activity requires its binding with CREB-binding protein (CBP) after CREB is phosphorylated at Ser133. The domains involved for CREB-CBP interaction are kinase-inducible domain (KID) from CREB and KID-interacting domain (KIX) from CBP. Recent studies suggest that CREB is an attractive target for novel cancer therapeutics. To identify novel chemotypes as inhibitors of KIX-KID interaction, we screened the NCI-diversity set of compounds using a split renilla luciferase assay and identified 2-[(7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio]pyridine 1-oxide (compound 1, NSC228155) as a potent inhibitor of KIX-KID interaction. However, compound 1 was not particularly selective against CREB-mediated gene transcription in living HEK 293T cells. Further structure-activityrelationship studies identified 4-aniline substituted nitrobenzofurazans with improved selectivity.

Original languageEnglish (US)
Pages (from-to)5371-5375
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number19
StatePublished - Oct 1 2013


  • CBP
  • CREB
  • Cancer
  • Inhibitor
  • Screening
  • Selectivity
  • Structure-activity relationships

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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