Boron-Based Inhibitors of Acyl Protein Thioesterases 1 and 2

Tobias J. Zimmermann; Marco Bürger; Etsu Tashiro; Yasumitsu Kondoh; Nancy E. Martinez; Kristina Görmer; Sigrid Rosin-Steiner; Takeshi Shimizu; Shoichiro Ozaki; Katsuhiko Mikoshiba; Nobumoto Watanabe; Dennis Hall; Ingrid R. Vetter; Hiroyuki Osada; Christian Hedberg; Herbert Waldmann

doi:10.1002/cbic.201200571

Boron-Based Inhibitors of Acyl Protein Thioesterases 1 and 2

Tobias J. Zimmermann, Marco Bürger, Etsu Tashiro, Yasumitsu Kondoh, Nancy E. Martinez, Kristina Görmer, Sigrid Rosin-Steiner, Takeshi Shimizu, Shoichiro Ozaki, Katsuhiko Mikoshiba, Nobumoto Watanabe, Dennis Hall, Ingrid R. Vetter, Hiroyuki Osada, Christian Hedberg, Herbert Waldmann

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

28 Citations (Scopus)

Abstract

Ras proteins are of importance in cell proliferation, and hence their mutated forms play causative roles in many kinds of cancer in different tissues. Inhibition of the Ras-depalmitoylating enzyme acyl protein thioesterases APT1 and -2 is a new approach to modulating the Ras cycle. Here we present boronic and borinic acid derivatives as a new class of potent and nontoxic APT inhibitors. These compounds were detected by extensive library screening using chemical arrays and turned out to inhibit human APT1 and -2 in a competitive mode. Furthermore, one of the molecules was demonstrated to inhibit Erk1/2 phosphorylation significantly.

Original language	English
Pages (from-to)	115-122
Number of pages	8
Journal	ChemBioChem
Volume	14
Issue number	1
DOIs	https://doi.org/10.1002/cbic.201200571
Publication status	Published - 2013 Jan
Externally published	Yes

Keywords

Acyl protein thioesterases
Boronic acids
Inhibitors
Microarrays
Oncogenic Ras proteins

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/cbic.201200571

Cite this

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title = "Boron-Based Inhibitors of Acyl Protein Thioesterases 1 and 2",

abstract = "Ras proteins are of importance in cell proliferation, and hence their mutated forms play causative roles in many kinds of cancer in different tissues. Inhibition of the Ras-depalmitoylating enzyme acyl protein thioesterases APT1 and -2 is a new approach to modulating the Ras cycle. Here we present boronic and borinic acid derivatives as a new class of potent and nontoxic APT inhibitors. These compounds were detected by extensive library screening using chemical arrays and turned out to inhibit human APT1 and -2 in a competitive mode. Furthermore, one of the molecules was demonstrated to inhibit Erk1/2 phosphorylation significantly.",

keywords = "Acyl protein thioesterases, Boronic acids, Inhibitors, Microarrays, Oncogenic Ras proteins",

author = "Zimmermann, {Tobias J.} and Marco B{\"u}rger and Etsu Tashiro and Yasumitsu Kondoh and Martinez, {Nancy E.} and Kristina G{\"o}rmer and Sigrid Rosin-Steiner and Takeshi Shimizu and Shoichiro Ozaki and Katsuhiko Mikoshiba and Nobumoto Watanabe and Dennis Hall and Vetter, {Ingrid R.} and Hiroyuki Osada and Christian Hedberg and Herbert Waldmann",

year = "2013",

month = jan,

doi = "10.1002/cbic.201200571",

language = "English",

volume = "14",

pages = "115--122",

journal = "ChemBioChem",

issn = "1439-4227",

publisher = "Wiley-VCH Verlag",

number = "1",

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T1 - Boron-Based Inhibitors of Acyl Protein Thioesterases 1 and 2

AU - Zimmermann, Tobias J.

AU - Bürger, Marco

AU - Tashiro, Etsu

AU - Kondoh, Yasumitsu

AU - Martinez, Nancy E.

AU - Görmer, Kristina

AU - Rosin-Steiner, Sigrid

AU - Shimizu, Takeshi

AU - Ozaki, Shoichiro

AU - Mikoshiba, Katsuhiko

AU - Watanabe, Nobumoto

AU - Hall, Dennis

AU - Vetter, Ingrid R.

AU - Osada, Hiroyuki

AU - Hedberg, Christian

AU - Waldmann, Herbert

PY - 2013/1

Y1 - 2013/1

N2 - Ras proteins are of importance in cell proliferation, and hence their mutated forms play causative roles in many kinds of cancer in different tissues. Inhibition of the Ras-depalmitoylating enzyme acyl protein thioesterases APT1 and -2 is a new approach to modulating the Ras cycle. Here we present boronic and borinic acid derivatives as a new class of potent and nontoxic APT inhibitors. These compounds were detected by extensive library screening using chemical arrays and turned out to inhibit human APT1 and -2 in a competitive mode. Furthermore, one of the molecules was demonstrated to inhibit Erk1/2 phosphorylation significantly.

AB - Ras proteins are of importance in cell proliferation, and hence their mutated forms play causative roles in many kinds of cancer in different tissues. Inhibition of the Ras-depalmitoylating enzyme acyl protein thioesterases APT1 and -2 is a new approach to modulating the Ras cycle. Here we present boronic and borinic acid derivatives as a new class of potent and nontoxic APT inhibitors. These compounds were detected by extensive library screening using chemical arrays and turned out to inhibit human APT1 and -2 in a competitive mode. Furthermore, one of the molecules was demonstrated to inhibit Erk1/2 phosphorylation significantly.

KW - Acyl protein thioesterases

KW - Boronic acids

KW - Inhibitors

KW - Microarrays

KW - Oncogenic Ras proteins

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U2 - 10.1002/cbic.201200571

DO - 10.1002/cbic.201200571

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AN - SCOPUS:84871479018

SN - 1439-4227

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SP - 115

EP - 122

JO - ChemBioChem

JF - ChemBioChem

IS - 1

ER -

Boron-Based Inhibitors of Acyl Protein Thioesterases 1 and 2

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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