Discodermolide analogues as the chemical component of combination bacteriolytic therapy

Amos B. Smith, B. Scott Freeze, Matthew J. LaMarche, Jason Sager, Kenneth W Kinzler, Bert Vogelstein

Research output: Contribution to journalArticle

Abstract

The marine natural product (+)-discodermolide (1) and several simplified analogues of this microtubule-stabilizing agent have proven to be potent in vitro cell growth inhibitory agents in several human cancer cell lines. Here, we demonstrate the in vivo efficacy of discodermolide and several simplified congeners, both as stand-alone anti-tumor agents and, in the case of (+)-2,3-anhydrodiscodermolide (3), as a chemical component of the combination bacteriolytic therapy. A single intravenous injection of (+)-3 plus genetically modified Clostridium novyi-NT spores caused rapid and complete regressions of tumors in mice bearing HCT116 colorectal cancer xenografts.

Original languageEnglish (US)
Pages (from-to)3623-3626
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume15
Issue number15
DOIs
StatePublished - Aug 1 2005

Fingerprint

Tumors
Bearings (structural)
Clostridium
Excipients
Cell growth
Biological Products
Heterografts
Neoplasms
Cells
Spores
Intravenous Injections
Microtubules
Colorectal Neoplasms
Therapeutics
Cell Line
Growth
discodermolide
In Vitro Techniques

Keywords

  • Bacteriolytic
  • COBALT
  • Discodermolide
  • Microtubule-stabilizing

ASJC Scopus subject areas

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

Cite this

Discodermolide analogues as the chemical component of combination bacteriolytic therapy. / Smith, Amos B.; Freeze, B. Scott; LaMarche, Matthew J.; Sager, Jason; Kinzler, Kenneth W; Vogelstein, Bert.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 15, No. 15, 01.08.2005, p. 3623-3626.

Research output: Contribution to journalArticle

Smith, Amos B. ; Freeze, B. Scott ; LaMarche, Matthew J. ; Sager, Jason ; Kinzler, Kenneth W ; Vogelstein, Bert. / Discodermolide analogues as the chemical component of combination bacteriolytic therapy. In: Bioorganic and Medicinal Chemistry Letters. 2005 ; Vol. 15, No. 15. pp. 3623-3626.
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