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Boron‐Based Inhibitors of Acyl Protein Thioesterases 1 and 2
Author(s) -
Zimmermann Tobias J.,
Bürger Marco,
Tashiro Etsu,
Kondoh Yasumitsu,
Martinez Nancy E.,
Görmer Kristina,
RosinSteiner Sigrid,
Shimizu Takeshi,
Ozaki Shoichiro,
Mikoshiba Katsuhiko,
Watanabe Nobumoto,
Hall Dennis,
Vetter Ingrid R.,
Osada Hiroyuki,
Hedberg Christian,
Waldmann Herbert
Publication year - 2013
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201200571
Subject(s) - chemistry , biochemistry , enzyme , boronic acid , phosphorylation , combinatorial chemistry
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.