NSC405020 is a PEX inhibitor. NSC405020 repressed migration of 184B5-MT cells on COL-I in a dose-dependent manner at concentration ranging in 25-100μM. It directly interacted with PEX in the full-length MT1-MMP structure and that these interactions affected PEX homodimerization. NSC405020 did not inhibit the catalytic function of cellular MT1-MMP or the catalytic activity of MMP-2. NSC 405020 at concentration of 400μM did not show any cytotoxicity in MCF7-β3/MT cells in vitro. However, injection with NSC405020 at 0.5mg/kg 3 times per week for 7 injections inhibited MCF7-β3/MT tumor growth in vivo, and repressed the collagenolytic function of PEX[2].
作用机制
Binding of NSC405020 affected the conformation and flexibility of blades I to IV of the β-propeller and, as a result, decreased the PEX-dependent homodimerization of cellular MT1-MMP.[2]
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