Dehydroacetic acid (DHAA) and derivative for uses in treating cancer

Patent metadata

Field	Value
Publication number	US-10792274-B2
Application number	US-201916386763-A
Country	US
Kind code	B2
Filing date	Apr 17, 2019
Priority date	Nov 4, 2016
Publication date	Oct 6, 2020
Grant date	Oct 6, 2020

Abstract

This disclosure relates to methods of managing or treating cancer with agents that lower circulating acetoacetate levels, such as hypolipidemic agents, or other agents that antagonize acetoacetate-BRAF V600 mutant binding to attenuate BRAF V600 mutant tumor growth. In certain embodiments, this disclosure relates to methods of treating cancer comprising administering an effective amount of an agent to a subject in need thereof, wherein the agent is dehydroacetic acid, derivative, prodrug, or salt thereof.

First claim

The invention claimed is:

1. A method of treating cancer or a neoplasm comprising administering an effective amount of dehydroacetic acid, or its derivative, or their salts thereof to a subject in need thereof,
wherein the dehydroacetic acid derivative is of the following formula:

wherein,
W is O;
X is O, S, or NH;
Y is O, S, or NH;
Z is OH, SH, or NH 2 optionally substituted with one or more, the same or different R 10 ;
R 1 is hydrogen, halogen, alkyl, halogenated alkyl, formyl, carboxy, hydroxyalkyl, thioalkyl, aminoalkyl, alkanoyl, alkoxycarbonyl, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, benzoyl, benzyl, aryl, or heterocyclyl, wherein R 1 is optionally substituted with one or more, the same or different R 10 ;
R 2 is hydrogen, halogen, alkyl, halogenated alkyl, formyl, carboxy, hydroxyalkyl, thioalkyl, aminoalkyl, alkanoyl, alkoxycarbonyl, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, benzoyl, benzyl, aryl, or heterocyclyl, wherein R 2 is optionally substituted with one or more, the same or different R 10 ;
R 3 is hydrogen, alkyl, halogenated alkyl, formyl, carboxy, hydroxyalkyl, thioalkyl, aminoalkyl, alkanoyl, alkoxycarbonyl, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, benzoyl, benzyl, aryl, or heterocyclyl, wherein R 3 is optionally substituted with one or more, the same or different R 10 ; and
R 10 is alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, hydroxyalkyl, alkylthio, thioalkyl, alkylamino, aminoalkyl, (alkyl) 2 amino, alkanoyl, alkoxycarbonyl, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, benzoyl, benzyl, aryl, or heterocyclyl, wherein R 10 is optionally substituted with one or more, the same or different R 11 ; and
R 11 is halogen, nitro, cyano, hydroxy, trifluoromethoxy, trifluoromethyl, amino, formyl, carboxy, carbamoyl, mercapto, sulfamoyl, methyl, ethyl, methoxy, ethoxy, isopropoxy, tert-butoxy, hydroxymethyl, hydroxyethyl, thiomethyl, thioethyl, aminomethyl, aminoethyl, acetyl, acetoxy, methylamino, ethylamino, dimethylamino, diethylamino, N-methyl-N-ethylamino, acetylamino, N-methylcarbamoyl, N-ethylcarbamoyl, N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-methyl-N-ethylcarbamoyl, methylthio, ethylthio, methylsulfinyl, ethylsulfinyl, mesyl, ethylsulfonyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, N-methylsulfamoyl, N-ethylsulfamoyl, N,N-dimethylsulfamoyl, N,N-diethylsulfamoyl, N-methyl-N-ethylsulfamoyl, benzoyl, benzyl, carbocyclyl, aryl, or heterocyclyl.

2. The method of claim 1 , wherein the neoplasm has a mutation encoding a V600E amino acid substitution present in the coding sequence for B-Raf.

3. The method of claim 1 , wherein the subject is suffering from metastatic melanoma.

4. The method of claim 1 , wherein dehydroacetic acid, or its derivative, or their salts thereof is administered in combination with a second therapeutic agent.

Assignees

• Univ Emory
• Us Gov Veterans Affairs

Inventors

• Chen Jing
• Arbiser Jack
• Pollack Brian
• Xia Siyuan

Classifications

• A61K31/351 Primary

  not condensed with another ring · CPC title