Patent ID: 9182402
Filing Date: 2015-11-10
Classification: A61K,A61P,C12N,G01N

Abstract:
1. A method for determining cancer progression or metastasis of a cancer that is characterized by cancer cells in which hepsin overexpression is present, comprising: (a) contacting (i) a hepsin inhibitor with (ii) a cancer cell that comprises a cell surface hepsin polypeptide, under conditions and for a time sufficient for the hepsin inhibitor to physically contact the cell surface hepsin polypeptide and thereby inhibit hepsin proteolytic activity on the cell surface, wherein the hepsin inhibitor is detectable by radiological imaging, fluorescence magnetic resonance imaging, immunofluorescence imaging, immunohistologic imaging, immunologic detection, biochemical detection or histochemical detection; and (b) detecting the hepsin inhibitor by radiological imaging, fluorescence magnetic resonance imaging, immunofluorescence imaging, immunohistologic imaging, immunologic detection, biochemical detection or histochemical detection, and thereby determining cancer progression or metastasis, wherein the cell surface hepsin polypeptide is selected from the group consisting of: (i) a cell surface polypeptide comprising the amino acid sequence set forth in any one of SEQ ID NOS:1, 6 and 9, (ii) a cell surface polypeptide comprising an amino acid sequence that is at least 85%, 90% or 95% identical to the polypeptide of (i) and that is capable of specific enzymatic cleavage of a chromogenic serine protease substrate that comprises L-pyroglutamyl-L-prolyl-L-arginine-p-nitroaniline hydrochloride (Glu-Pro-Arg-pNA), and (iii) a cell surface polypeptide that comprises a hepsin catalytic domain or a functional fragment thereof, said hepsin catalytic domain or functional fragment thereof comprising an amino acid sequence that is at least 80%; 85%, 90% or 95% identical to the amino acid sequence set forth in any one of SEQ ID NOS:5, 8 and 11 and that is capable of specific enzymatic cleavage of a chromogenic serine protease substrate that comprises L-pyroglutamyl-L-prolyl-L-arginine-p-nitroaniline hydrochloride (pyroGlu-Pro-Arg-pNA), and wherein the hepsin inhibitor comprises at least one compound that is selected from a compound of formula (IV), a compound of formula (V) and a compound of formula (VIII): wherein: each k is 1, 2 or 3; each m is 1 or 2; each n is 1, 2, 3, 4 or 5; each r is 1, 2, 3 or 4; q is 1, 2, 3, 4, 5 or 6; each R each R each R each R as a single stereoisomer or a mixture thereof; or a pharmaceutically acceptable salt thereof.