METHOD OF USING SUBSTRATES OF AKR1Bl/AKR1B10 AS ANTI-CANCER DRUGS

Abstract

The present disclosure relates to, inter alia, a method of treating cancer in a human patient in need thereof, comprising administering a therapeutically effective amount of a substrate of AKR1B1, AKR1B10, or both to said patient, wherein said patient has, or is suspected to have, cancer cells with elevated levels of AKR1B1, AKR1B10, or both, wherein said substrate is not 2-deoxy-D-glucose.

1 . A method of treating cancer in a human patient in need thereof, comprising administering a therapeutically effective amount of a substrate of AKR1B 1, AKR1B 10, or both, to said patient, wherein said patient has, or is suspected to have, cancer cells with elevated levels of AKR1B 1, AKR1B 10, or both, wherein said substrate is not 2-deoxy-D-glucose. 
     
     
         2 . The method of treating of  claim 1 , further comprising administering a therapeutically effective amount of an inhibitor of reduced glutathione (GSH) to said patient. 
     
     
         3 . A method of treating cancer in a human patient in need thereof, comprising administering to said patient a therapeutically effective amount of an activator of AKR1B 1 enzyme level or activity, AKR1B10 enzyme level or activity, or the enzyme level or activity of both, in a cancer cell and a therapeutically effective amount of a substrate of AKR1B 1, AKR1B 10, or both to said patient, wherein said substrate is not 2-deoxy-D-glucose. 
     
     
         4 . The method of  claim 1 , further comprising administering to the patient a therapeutically effective amount of an activator of AKR1B 1 enzyme level or activity, AKR1B10 enzyme level or activity, or the enzyme level or activity of both. 
     
     
         5 . The method of  claim 3 , further comprising administering to the patient an inhibitor of reduced glutathione (GSH). 
     
     
         6 . The method of  claim 2 , wherein the inhibitor of GSH is L-buthionine-[S,R]-sulfoximine (BSO). 
     
     
         7 . The method of  claim 1 , wherein the substrate is D-Galactose, DL-Glyceraldehyde, Diacetyl, Methyglyoxal, Pyridine-2-aldehyde, p-Nitrobenzaldehyde, Pyruvic acid, Progesterone, Prostaglandin E, methyl glyoxal, or 4-hydroxynonenal . 
     
     
         8 . The method of  claim 4 , wherein the activator of AKR1B1 enzyme level or activity, AKR1B10 enzyme level or activity, or the enzyme level or activity of both is MG-132 or bortezomib. 
     
     
         9 . The method of  claim 1 , wherein the patient is being treated with one or more other anti-cancer therapy or therapeutic agent. 
     
     
         10 . The method of  claim 9 , wherein radiation therapy is one of the one or more other anti-cancer therapy. 
     
     
         11 . The method of  claim 1 , wherein the cancer is liver, prostate, breast, ovarian, cervical, rectal, lung, or oral cancer. 
     
     
         12 . The method of  claim 1 , wherein the substrate is Glyceraldehyde. 
     
     
         13 . The method of  claim 1 , wherein the substrate is Diacetyl. 
     
     
         14 . The method of  claim 5 , wherein the inhibitor of GSH is L-buthionine-[S,R]-sulfoximine (BSO). 
     
     
         15 . The method of  claim 3 , wherein the substrate is D-Galactose, DL-Glyceraldehyde, Diacetyl, Methyglyoxal, Pyridine-2-aldehyde, p-Nitrobenzaldehyde, Pyruvic acid, Progesterone, Prostaglandin E, methyl glyoxal, or 4-hydroxynonenal. 
     
     
         16 . The method of  claim 3 , wherein the activator of AKR1B 1 enzyme level or activity, AKR1B10 enzyme level or activity, or the enzyme level or activity of both is MG-132 or bortezomib. 
     
     
         17 . The method of  claim 3 , wherein the patient is being treated with one or more other anti-cancer therapy or therapeutic agent. 
     
     
         18 . The method of  claim 17 , wherein radiation therapy is one of the one or more other anti-cancer therapy. 
     
     
         19 . The method of  claim 3  wherein the cancer is liver, prostate, breast, ovarian, cervical, rectal, lung, or oral cancer. 
     
     
         20 . The method of  claim 3 , wherein the substrate is Glyceraldehyde or Diacetyl.