Methods of using pyruvate kinase activators

Abstract

Described herein are methods for using compounds that activate pyruvate kinase.

1 - 40 . (canceled) 
     
     
         41 . A method for activating one or more isozymes of pyruvate kinase in a subject in need thereof, comprising orally administering to the subject once or twice daily a dose of about 10 mg to about 60 mg or about 60 mg to about 200 mg of (1) Compound 1 or a pharmaceutically acceptable salt or hydrate thereof; or (2) a pharmaceutical composition comprising Compound 1 or a pharmaceutically acceptable salt or hydrate thereof, and a pharmaceutically acceptable carrier, to thereby activate pyruvate kinase in the subject, wherein Compound 1 is N-(4-(4-(cyclopropylmethyl)piperazine-1-carbonyl)phenyl)quinoline-8-sulfonamide. 
     
     
         42 . The method of  claim 41 , wherein the method comprises orally administering to the subject once or twice daily a dose of about 10 mg to about 60 mg of Compound 1. 
     
     
         43 . The method of  claim 41 , wherein the method comprises orally administering to the subject once or twice daily a dose of about 60 mg to about 200 mg of Compound 1. 
     
     
         44 . The method of  claim 41 , wherein the method comprises orally administering to the subject once or twice daily a dose of about 30 mg or about 120 mg of Compound 1. 
     
     
         45 . The method of  claim 41 , wherein the method comprises orally administering to the subject once or twice daily a dose of about 50 mg, about 75 mg, about 100 mg, about 125 mg, about 150 mg, about 175 mg or about 200 mg of Compound 1. 
     
     
         46 . The method of  claim 41 , wherein the method comprises orally administering Compound 1 once daily. 
     
     
         47 . The method of  claim 41 , wherein the method comprises orally administering Compound 1 twice daily. 
     
     
         48 . The method of  claim 41 , wherein the method comprises orally administering Compound 1 at a dose of about 15 mg about every 12 hours, about 60 mg about every 12 hours, or about 120 mg about every 12 hours. 
     
     
         49 . The method of  claim 41 , wherein the method comprises orally administering Compound 1 at a dose of about 10 mg to about 60 mg about every 12 hours, or about 60 mg to about 200 mg about every 12 hours. 
     
     
         50 . The method of  claim 41 , wherein the method comprises orally administering Compound 1 at a dose of about 10 mg to about 60 mg about every 12 hours, or about 60 mg to about 200 mg about every 12 hours. 
     
     
         51 . The method of  claim 41 , wherein the method comprises orally administering Compound 1 at a dose of about 60 mg to about 200 mg about every 24 hours. 
     
     
         52 . The method of  claim 41 , wherein the method comprises orally administering Compound 1 at a dose of about 90 mg about every 24 hours, about 120 mg about every 24 hours, about 150 mg about every 24 hours, about 180 mg about every 24 hours, or about 200 mg about every 24 hours. 
     
     
         53 . The method of  claim 41 , wherein the one or more isozymes of pyruvate kinase is selected from PKR, PKM2, and PKL. 
     
     
         54 . A method for activating one or more isozymes of pyruvate kinase in a subject in need thereof, comprising orally administering to the subject once or twice daily a dose of about 50 mg to about 300 mg of (1) Compound 1 or a pharmaceutically acceptable salt or hydrate thereof; or (2) a pharmaceutical composition comprising Compound 1 or a pharmaceutically acceptable salt or hydrate thereof, and a pharmaceutically acceptable carrier, to thereby activate pyruvate kinase in the subject, wherein Compound 1 is N-(4-(4-(cyclopropylmethyl)piperazine-1-carbonyl)phenyl)quinoline-8-sulfonamide. 
     
     
         55 . The method of  claim 54 , wherein the method comprises orally administering to the subject once or twice daily a dose of about 225 mg, about 250 mg, about 275 mg, or about 300 mg of Compound 1. 
     
     
         56 . The method of  claim 54 , wherein the method comprises orally administering Compound 1 twice daily. 
     
     
         57 . The method of  claim 54 , wherein the method comprises orally administering twice daily a dose of about 50 mg of Compound 1. 
     
     
         58 . The method of  claim 54 , wherein the method comprises orally administering twice daily a dose of about 100 mg of Compound 1. 
     
     
         59 . The method of  claim 54 , wherein the one or more isozymes of pyruvate kinase is selected from PKR, PKM2, and PKL.