Boron-based inhibitors of acyl protein thioesterases 1 and 2.
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.
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GENE-N GENE-N GENE-N GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-N GENE-N GENE-N
APT human APT1 and -2 Erk1/2 acyl protein thioesterases 1 and 2 acyl boronic borinic acid Boron acyl Ras Ras acyl protein thioesterases APT1 and -2 Ras