881487-77-0

KPT-6566 is a selective and covalent prolyl isomerase PIN1 inhibitor, covalently binds to the catalytic site of PIN1, selectively inhibits and degrades PIN1. KPT-6566 shows an IC50 value of 640 nM and a Ki value of 625.2 nM for PIN1 PPIase domain. KPT-6566 can be used for the research of cancer[1].

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 modificationresulting in Pin1 degradation and the release of ROS-generating and DNA-damaging quinone-mimicking KPT-6566-B. KPT-6566 inhibits the proliferation of wild-typebut 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.

[1] Campaner E, et al. A covalent PIN1 inhibitor selectively targets cancer cells by a dual mechanism of action. Nat Commun. 2017 Jun 9;8:15772. DOI:10.1038/ncomms15772