Methoxychalcone inhibitors of androgen receptor translocation and function

Yeong Sang Kim; Vineet Kumar; Sunmin Lee; Aki Iwai; Len Neckers; Sanjay V. Malhotra; Jane B. Trepel

doi:10.1016/j.bmcl.2011.12.141

Methoxychalcone inhibitors of androgen receptor translocation and function

Yeong Sang Kim, Vineet Kumar, Sunmin Lee, Aki Iwai, Len Neckers, Sanjay V. Malhotra, Jane B. Trepel

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

19 Scopus citations

Abstract

Androgen receptor activity drives incurable castrate-resistant prostate cancer. All approved antiandrogens inhibit androgen receptor-driven transcription, and in addition the second-generation antiandrogen MDV3100 inhibits ligand-activated androgen receptor nuclear translocation, via an unknown mechanism. Here, we report methoxychalcones that lock the heat shock protein 90-androgen receptor complex in the cytoplasm in an androgen-non- responsive state, thus demonstrating a novel chemical scaffold for antiandrogen development and a unique mechanism of antiandrogen activity.

Original language	English (US)
Pages (from-to)	2105-2109
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	22
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2011.12.141
State	Published - Mar 1 2012
Externally published	Yes

Keywords

Androgen receptor translocation
Antiandrogen
Chalcone
Hsp90
Prostate cancer

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.2011.12.141

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title = "Methoxychalcone inhibitors of androgen receptor translocation and function",

abstract = "Androgen receptor activity drives incurable castrate-resistant prostate cancer. All approved antiandrogens inhibit androgen receptor-driven transcription, and in addition the second-generation antiandrogen MDV3100 inhibits ligand-activated androgen receptor nuclear translocation, via an unknown mechanism. Here, we report methoxychalcones that lock the heat shock protein 90-androgen receptor complex in the cytoplasm in an androgen-non- responsive state, thus demonstrating a novel chemical scaffold for antiandrogen development and a unique mechanism of antiandrogen activity.",

keywords = "Androgen receptor translocation, Antiandrogen, Chalcone, Hsp90, Prostate cancer",

author = "Kim, {Yeong Sang} and Vineet Kumar and Sunmin Lee and Aki Iwai and Len Neckers and Malhotra, {Sanjay V.} and Trepel, {Jane B.}",

note = "Funding Information: V.K. and S.V.M. would like to thank the National Cancer Institute (NCI) Developmental Therapeutics Program. This project has been funded in whole or in part with federal funds from the NCI, National Institutes of Health, to the Intramural Research Program (Y.S.K., A.I., S.L., L.N., and J.B.T.), and to DTP NCI-Frederick SAIC, under Contract No. HSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. ",

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doi = "10.1016/j.bmcl.2011.12.141",

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T1 - Methoxychalcone inhibitors of androgen receptor translocation and function

AU - Kim, Yeong Sang

AU - Kumar, Vineet

AU - Lee, Sunmin

AU - Iwai, Aki

AU - Neckers, Len

AU - Malhotra, Sanjay V.

AU - Trepel, Jane B.

N1 - Funding Information: V.K. and S.V.M. would like to thank the National Cancer Institute (NCI) Developmental Therapeutics Program. This project has been funded in whole or in part with federal funds from the NCI, National Institutes of Health, to the Intramural Research Program (Y.S.K., A.I., S.L., L.N., and J.B.T.), and to DTP NCI-Frederick SAIC, under Contract No. HSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

PY - 2012/3/1

Y1 - 2012/3/1

N2 - Androgen receptor activity drives incurable castrate-resistant prostate cancer. All approved antiandrogens inhibit androgen receptor-driven transcription, and in addition the second-generation antiandrogen MDV3100 inhibits ligand-activated androgen receptor nuclear translocation, via an unknown mechanism. Here, we report methoxychalcones that lock the heat shock protein 90-androgen receptor complex in the cytoplasm in an androgen-non- responsive state, thus demonstrating a novel chemical scaffold for antiandrogen development and a unique mechanism of antiandrogen activity.

AB - Androgen receptor activity drives incurable castrate-resistant prostate cancer. All approved antiandrogens inhibit androgen receptor-driven transcription, and in addition the second-generation antiandrogen MDV3100 inhibits ligand-activated androgen receptor nuclear translocation, via an unknown mechanism. Here, we report methoxychalcones that lock the heat shock protein 90-androgen receptor complex in the cytoplasm in an androgen-non- responsive state, thus demonstrating a novel chemical scaffold for antiandrogen development and a unique mechanism of antiandrogen activity.

KW - Androgen receptor translocation

KW - Antiandrogen

KW - Chalcone

KW - Hsp90

KW - Prostate cancer

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Methoxychalcone inhibitors of androgen receptor translocation and function

Abstract

Keywords

ASJC Scopus subject areas

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