Exploitation of heparanase inhibitors from microbial metabolites. Using an efficient visual screening system

Keisuke Ishida, Takayuki Teruya, Siro Simizu, Hiroyuki Osada

Research output: Contribution to journalArticle

12 Citations (Scopus)


In this paper we describe the establishment of an efficient visual method for screening heparanase inhibitors, and we present the results of screening 10,000 microbial culture broths. Heparanase-overexpressing stable clones of the human hepatocellular carcinoma HepG2 cells were established and used as an enzyme source. Digestion of heparan sulfate (HS) was detected using novel HS-containing tablets or SDS-polyacrylamide gel electrophoresis. This method was able to find suramin, a known heparanase inhibitors, from a library of typical enzyme inhibitors. By screening 10,000 culture broths of microorganism (actinomycetes, fungi, and bacteria) an actinomycete strain, RK99-A234, was found to have haparanase inhibitory activity. RK-682 was identified in the fermentation broths as a heparanase inhibitors, IC50 = 17 μM.

Original languageEnglish
Pages (from-to)136-142
Number of pages7
JournalJournal of Antibiotics
Issue number2
Publication statusPublished - 2004 Feb


ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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