2-[[4-[[[4-(tert-Butyl)phenyl]sulfonyl]imino]-1-oxo-1,4-dihydro-2-naphthyl]thio]acetic Acid

Potent and selective peptidyl-prolyl cis-trans isomerase (PPIase) Pin1 covalent inhibitor with anti-cancer efficacy in cultures and in vivo.

KPT-6566 is a potent and selective peptidyl-prolyl cis-trans isomerase (PPIase) Pin1 inhibitor (IC50 = 640 nM) th at targets Pin1 catalytic site for covalent modification, resulting in Pin1 degradation and the release of ROS-generating and DNA-damaging quinone-mimicking KPT-6566-B. KPT-6566 inhibits the proliferation of wild-type, but not Pin1-/-, MEFs (1-5 μM for 48h) with concomitant reduction of cellular pRB and Cyclin D1 hyperphosphorylation. KPT-6566 induces cancer cell death in cultures (1-10 μM for 48h) and reduces MDA-MB-231 lung metastasis in mice in vivo (5 mg/kg/d i.p.). KPT-6566 is more potent than juglone and does not affect the PPIase activity of GST-FKBP4 or GST-PPIA.