Lockdown is a selective, reversible and non-competitive inhibitor of the integrin phosphatase PPM1F (IC50=16.37 uM), blocks cancer cell invasion.
Lockdown acts in a dose-dependent, allosteric manner with high selectivity for PPM1F.
Lockdown does not inhibit other protein phosphatases (PTP1P, PTPRJ, PP5) in vitro and does not induce additional phenotypes in PPM1F knockout cells.
Lockdown fully re-capitulated the phenotype of PPM1F-deficient cells, increased phosphorylation of PPM1F substrates and corruption of integrin-dependent cellular processes in Lockdown treated glioblastoma cells.
Phosphatase PPM1F is a regulator of cell adhesion by fine-tuning integrin activity and actin cytoskeleton structures. Elevated expression of this enzyme in human tumors is associated with high invasiveness, enhanced metastasis, and poor prognosis.
