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

doi:10.1016/j.bmcl.2005.05.068

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

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	https://doi.org/10.1016/j.bmcl.2005.05.068
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

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10.1016/j.bmcl.2005.05.068

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title = "Discodermolide analogues as the chemical component of combination bacteriolytic therapy",

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.",

keywords = "Bacteriolytic, COBALT, Discodermolide, Microtubule-stabilizing",

author = "Smith, {Amos B.} and Freeze, {B. Scott} and LaMarche, {Matthew J.} and Jason Sager and Kinzler, {Kenneth W.} and Bert Vogelstein",

note = "Funding Information: Financial support was provided by the National Institutes of Health (Institute of General Medical Sciences) through Grant GM-29028, the Department of the Army through Grant DAMD 17-00-1-0404, through Grant CA 62924 from the National Cancer Institute, through a gift from the Miracle Foundation, and through a Sponsored Research Agreement between the University of Pennsylvania and Kosan Biosciences, Inc., where Professor Smith is a member of the Scientific Advisory Board.",

year = "2005",

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doi = "10.1016/j.bmcl.2005.05.068",

language = "English (US)",

volume = "15",

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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

N1 - Funding Information: Financial support was provided by the National Institutes of Health (Institute of General Medical Sciences) through Grant GM-29028, the Department of the Army through Grant DAMD 17-00-1-0404, through Grant CA 62924 from the National Cancer Institute, through a gift from the Miracle Foundation, and through a Sponsored Research Agreement between the University of Pennsylvania and Kosan Biosciences, Inc., where Professor Smith is a member of the Scientific Advisory Board.

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

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

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ER -

Discodermolide analogues as the chemical component of combination bacteriolytic therapy

Abstract

Keywords

ASJC Scopus subject areas

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