Par4 inhibitor therapy for patients with par4 polymorphism

Abstract

Disclosed herein are methods for determining whether a PAR4 inhibitor should be administered to a human subject, the methods comprising administering a PAR4 inhibitor to a subject determined to have a “G” allele for a single-nucleotide polymorphism (SNP) at rs773902, and not administering a PAR4 inhibitor to a subject determined to have an “A” allele for the SNP at rs773902. A genotyping assay can be used to determine the SNP.

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         9 . A method of preventing or treating thrombosis in a human subject who is (a) being administered a P2Y12 inhibitor and (b) has a “G” allele for a single-nucleotide polymorphism (SNP) at rs773902; the method comprising (a) stopping administration of the P2Y12 inhibitor and (b) administering a therapeutically effective amount of a PAR4 inhibitor. 
     
     
         10 . The method of  claim 9 , wherein the PAR4 inhibitor is a compound as disclosed in WO 13/163244 (e.g., compound of any one of Examples 1-428). 
     
     
         11 . The method of  claim 9 , wherien the PAR4 inhibitor is selected from the group consisting of ethyl 4-(1-benzyl-1H-indazol-3-yl)benzoate (YD-3), trans-cinnamoyl-YPGKF-amide, P4pal-il, and palmitoyl-SGRRYGHALR-amide (P4pal-10). 
     
     
         12 . The method of  claim 9 , wherein the thrombosis is associated with coronary artery disease, stroke, vascular thrombosis, arterial thrombosis, atherothrombosis, deep vein thrombosis, peripheral vascular disease, peripheral arterial disease, or an inflammatory disease. 
     
     
         13 . The method of  claim 9 , further comprising testing a sample from the human subject to determine the genotype of the SNP at rs773902. 
     
     
         14 . The method of  claim 13 , wherein the sample is a blood sample, a urine sample, a buccal sample, a saliva sample, or a hair sample. 
     
     
         15 . The method of  claim 9 , further comprising administering a therapeutically effective amount of a P2Y12 inhibitor to the subject selected from the group consisting of clopidogrel, prasugrel, ticagrelor, or cangrelor, a salt thereof, or combinations thereof. 
     
     
         16 . The method  claim 9 , further comprising administering a therapeutically effective amount of aspirin to the human subject. 
     
     
         17 . A method of preventing or treating thrombosis in a human subject comprising: (a) subjecting a test sample obtained from the human subject to a genotyping assay adapted to determine the genotype of the SNP at rs773902; (b) determining whether the polymorphism at rs773902 has a “G” allele or an “A” allele, and (c) administering to a patient having a “G allele a PAR4 inhibitor and administering to said patient with the “A” allele a therapeutic that is not a PAR4 inhibitor. 
     
     
         18 . The method of  claim 17 , wherien the PAR4 inhibitor is selected from the group consisting of ethyl 4-(1-benzyl-1H-indazol-3-yl)benzoate (YD-3), trans-cinnamoyl-YPGKF-amide, P4pal-il, and palmitoyl-SGRRYGHALR-amide (P4pal-10). 
     
     
         19 . The method of  claim 17 , further comprising administering a therapeutically effective amount of a P2Y12 inhibitor to the subject selected from the group consisting of clopidogrel, prasugrel, ticagrelor, or cangrelor, a salt thereof, or combinations thereof 
     
     
         20 . The method  claim 17 , further comprising administering a therapeutically effective amount of aspirin to the human subject.