NPEdia (re-discovered compound)
Producing organism
Streptomyces sp.
Biological activity
tubulin disassembler
The biological effects of pironetin and its derivatives on cell cycle progression and antitumor activity were studied. At 10-20 ng/ml, both pironetin and its demethyl derivative, NK10958P completely inhibited the cell proliferation of 3Y1 cells, however, epoxypironetin showed only a weak inhibitory activity. The cell cycle analysis revealed that these compounds arrested the cell cycle progression at the M-phase in a dose-dependent manner. These antiproliferative effects of pironetin were also observed in the range 5-25 ng/ml with several tumor cell lines. In CDF1-SLC mice bearing P388 leukemia cells, the intraperitoneal administration of 6.3 mg/kg pironetin over a 5-day period showed a moderate antitumor effect (T/C, 128%). As the chemical structure of pironetin is different from other M-phase inhibitors such as colchicine or vinblastine, pironetin will be the lead compound for a potential new antitumor drug.
isolation and structural determination
  • Kobayashi S, Tsuchiya K, Harada T, Nishide M, Kurokawa T, Nakagawa T, Shimada N, Kobayashi K.: Pironetin, a novel plant growth regulator produced by Streptomyces sp. NK10958. I. Taxonomy, production, isolation and preliminary characterization.
    J Antibiot, 47(6): 697-702 (1994) PMID: 8040075
  • Kobayashi S, Tsuchiya K, Kurokawa T, Nakagawa T, Shimada N, Iitaka Y.: Pironetin, a novel plant growth regulator produced by Streptomyces sp. NK10958. II. Structural elucidation.
    J Antibiot, 47(6): 703-707 (1994) PMID: 7794417
  • Kobayashi S, Tsuchiya K, Nishide M, Nishikiori T, Nakagawa T, Shimada N.: Pironetin, a novel plant growth regulator produced by Streptomyces sp. NK10958. III. Biosynthesis.
    J Antibiot, 48(8): 893-895 (1995) PMID: 7592038
  • biological activity as new roles
  • Kondoh M, Usui T, Kobayashi S, Tsuchiya K, Nishikawa K, Nishikiori T, Mayumi T, Osada H.: Cell cycle arrest and antitumor activity of pironetin and its derivatives.
    Cancer Lett, 126(1): 29-32 (1998) PMID: 9563645
  • Kondoh M, Usui T, Nishikiori T, Mayumi T, Osada H.: Apoptosis induction via microtubule disassembly by an antitumour compound, pironetin.
    Biochem J, 340( Pt 2): 411-416 (1999) PMID: 10333483
  • Simizu S, Shibasaki F, Osada H.: Bcl-2 inhibits calcineurin-mediated Fas ligand expression in antitumor drug-treated baby hamster kidney cells.
    Jpn J Cancer Res, 91(7): 706-714 (2000) PMID: 10920278
  • structure-activity relationship
  • Watanabe H, Watanabe H, Usui T, Kondoh M, Osada H, Kitahara T.: Synthesis of pironetin and related analogs: studies on structure-activity relationships as tubulin assembly inhibitors.
    J Antibiot, 53(5): 540-545 (2000) PMID: 10908119
  • Additional information