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) |
|---|---|
| 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 |
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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 journal › Article
}
TY - JOUR
T1 - Discodermolide analogues as the chemical component of combination bacteriolytic therapy
AU - Smith, Amos B.
AU - Freeze, B. Scott
AU - LaMarche, Matthew J.
AU - Sager, Jason
AU - Kinzler, Kenneth W
AU - Vogelstein, Bert
PY - 2005/8/1
Y1 - 2005/8/1
N2 - 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.
AB - 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.
KW - Bacteriolytic
KW - COBALT
KW - Discodermolide
KW - Microtubule-stabilizing
UR - http://www.scopus.com/inward/record.url?scp=21744455884&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=21744455884&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2005.05.068
DO - 10.1016/j.bmcl.2005.05.068
M3 - Article
VL - 15
SP - 3623
EP - 3626
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 15
ER -