ABD957 (ABD-957) is a potent, selective covalent inhibitor of the ABHD17 family of depalmitoylases, impairs N-Ras depalmitoylation in human AML cells.
ABD957 inhibits human ABHD17B (recombinantly expressed) with IC50 of 0.21 uM in lysates of HEK293T cells, does not inhibit LYPLA1, LYPLA2, or ABHD10.
ABD957 inhibits all three ABHD17s and partially impairs N-Ras depalmitoylation, ERK phosphorylation, and the growth of NRAS mutant cancer cells.
ABD957 stabilizes N-Ras palmitoylation less completely than Palm M, but is much more selective across the proteome.
ABD957 also impacted the subcellular distribution of N-Ras, leading to the accumulation of this protein at the plasma membrane.
ABD957 synergizes with MEK inhibition to block NRAS mutant cancer cell growth.
