GSK2830371 is an orally active, small-molecule inhibitor of metal-dependent Ser/Thr phosphatase PPM1D [1
]. Inhibition of PPM1D increases phosphorylation (inhibits dephosphorylation) of PPM1D substrates. GSK2830371 binds at an allosteric position close to PPM1D's catalytic site. Referred to as the 'flap' subdomain, this region is unique to PPM1D compared to other members of the PPM phosphatase family, and this confers PPM1D selectivity. GSK2830371 appears to be effective only in cell lines overexpressing PPM1D and with wild-type TP53
). Cell lines with mutant TP53
seem to be resistant to GSK2830371.