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 language | English (US) |
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Pages (from-to) | 3623-3626 |
Number of pages | 4 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 15 |
Issue number | 15 |
DOIs | |
State | Published - Aug 1 2005 |
Keywords
- Bacteriolytic
- COBALT
- Discodermolide
- Microtubule-stabilizing
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry