Potent non-benzoquinone ansamycin heat shock protein 90 inhibitors from genetic engineering of Streptomyces hygroscopicus

Hugo G. Menzella; Thomas Toan Tran; John R. Carney; Janice Lau-Wee; Jorge Galazzo; Christopher D. Reeves; Christopher Carreras; Sophie Mukadam; Sara Eng; Ziyang Zhong; Pieter B.M.W.M. Timmermans; Sumati Murli; Gary W. Ashley

doi:10.1021/jm900012a

Potent non-benzoquinone ansamycin heat shock protein 90 inhibitors from genetic engineering of Streptomyces hygroscopicus

Hugo G. Menzella, Thomas Toan Tran, John R. Carney, Janice Lau-Wee, Jorge Galazzo, Christopher D. Reeves, Christopher Carreras, Sophie Mukadam, Sara Eng, Ziyang Zhong, Pieter B.M.W.M. Timmermans, Sumati Murli, Gary W. Ashley

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

Abstract

Inhibition of the protein chaperone Hsp90 is a promising new approach to cancer therapy. We describe the preparation of potent non-benzoquinone ansamycins. One of these analogues, generated by feeding 3-amino-5-chlorobenzoic acid to a genetically engineered strain of Streptomyces hygroscopicus, shows high accumulation and long residence time in tumor tissue, is well-tolerated upon intravenous dosing, and is highly efficacious in the COLO205 mouse tumor xenograft model.

Original language	English (US)
Pages (from-to)	1518-1521
Number of pages	4
Journal	Journal of medicinal chemistry
Volume	52
Issue number	6
DOIs	https://doi.org/10.1021/jm900012a
State	Published - Mar 26 2009
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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Menzella, H. G., Tran, T. T., Carney, J. R., Lau-Wee, J., Galazzo, J., Reeves, C. D., Carreras, C., Mukadam, S., Eng, S., Zhong, Z., Timmermans, P. B. M. W. M., Murli, S., & Ashley, G. W. (2009). Potent non-benzoquinone ansamycin heat shock protein 90 inhibitors from genetic engineering of Streptomyces hygroscopicus. Journal of medicinal chemistry, 52(6), 1518-1521. https://doi.org/10.1021/jm900012a

Menzella, HG, Tran, TT, Carney, JR, Lau-Wee, J, Galazzo, J, Reeves, CD, Carreras, C, Mukadam, S, Eng, S, Zhong, Z, Timmermans, PBMWM, Murli, S & Ashley, GW 2009, 'Potent non-benzoquinone ansamycin heat shock protein 90 inhibitors from genetic engineering of Streptomyces hygroscopicus', Journal of medicinal chemistry, vol. 52, no. 6, pp. 1518-1521. https://doi.org/10.1021/jm900012a

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abstract = "Inhibition of the protein chaperone Hsp90 is a promising new approach to cancer therapy. We describe the preparation of potent non-benzoquinone ansamycins. One of these analogues, generated by feeding 3-amino-5-chlorobenzoic acid to a genetically engineered strain of Streptomyces hygroscopicus, shows high accumulation and long residence time in tumor tissue, is well-tolerated upon intravenous dosing, and is highly efficacious in the COLO205 mouse tumor xenograft model.",

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doi = "10.1021/jm900012a",

language = "English (US)",

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T1 - Potent non-benzoquinone ansamycin heat shock protein 90 inhibitors from genetic engineering of Streptomyces hygroscopicus

AU - Menzella, Hugo G.

AU - Tran, Thomas Toan

AU - Carney, John R.

AU - Lau-Wee, Janice

AU - Galazzo, Jorge

AU - Reeves, Christopher D.

AU - Carreras, Christopher

AU - Mukadam, Sophie

AU - Eng, Sara

AU - Zhong, Ziyang

AU - Timmermans, Pieter B.M.W.M.

AU - Murli, Sumati

AU - Ashley, Gary W.

PY - 2009/3/26

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N2 - Inhibition of the protein chaperone Hsp90 is a promising new approach to cancer therapy. We describe the preparation of potent non-benzoquinone ansamycins. One of these analogues, generated by feeding 3-amino-5-chlorobenzoic acid to a genetically engineered strain of Streptomyces hygroscopicus, shows high accumulation and long residence time in tumor tissue, is well-tolerated upon intravenous dosing, and is highly efficacious in the COLO205 mouse tumor xenograft model.

AB - Inhibition of the protein chaperone Hsp90 is a promising new approach to cancer therapy. We describe the preparation of potent non-benzoquinone ansamycins. One of these analogues, generated by feeding 3-amino-5-chlorobenzoic acid to a genetically engineered strain of Streptomyces hygroscopicus, shows high accumulation and long residence time in tumor tissue, is well-tolerated upon intravenous dosing, and is highly efficacious in the COLO205 mouse tumor xenograft model.

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Potent non-benzoquinone ansamycin heat shock protein 90 inhibitors from genetic engineering of Streptomyces hygroscopicus

Abstract

ASJC Scopus subject areas

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