Effective treatment of esophogeal adenocarcinoma using triciribine and related compounds
AssigneeUniversity of South Florida
InventorJin Q. Cheng
Life of this patent
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Abstract
The inventors have determined, contrary to the prior art and experience, how to successfully use triciribine to treat esophogeal adenocarcinoma by one or a combination of (i) administering triciribine only to patients which according to a diagnostic test described below, exhibit enhanced sensitivity to the drug; (ii) use of a described dosage level that minimizes the toxicity of the drug but yet still exhibits efficacy; or (iii) use of a described dosage regimen that minimizes the toxicity of the drug.
Claims20
A method for treating esophogeal adenocarcinoma in a mammal comprising treating the mammal with an effective amount of a compound of the formula:
- wherein each R2′, R3′ and R5′ are independently hydrogen, optionally substituted phosphate or phosphonate;
- acyl;
- alkyl;
- amide;
- sulfonate ester;
- sulfonyl, methanesulfonyl, benzylsulfonyl, arylsulfonyl, wherein the phenyl group is optionally substituted with one or more substituents;
- a lipid;
- a phospholipid;
- an amino acid;
- a carbohydrate;
- a peptide;
- or cholesterol;
- or other pharmaceutically acceptable leaving group that, in vivo, provides a compound wherein R2′, R3′ or R5′ is independently H or mono-, di- or tri-phosphate;
- wherein Rx and Ry are independently hydrogen, optionally substituted phosphate;
- acyl;
- amide, alkyl;
- aromatic, polyoxyalkylene;
- polyethyleneglycol, optionally substituted arylsulfonyl;
- a lipid;
- a phospholipid;
- an amino acid;
- a carbohydrate;
- a peptide;
- or cholesterol;
- or other pharmaceutically acceptable leaving group;
- wherein R1 and R2 each are independently H, optionally substituted straight chained, branched or cyclic alkyl, alkenyl, or alkynyl, CO-alkyl, CO-alkenyl, CO-alkynyl, CO-aryl or heteroaryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, sulfonyl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl.
A method of treating esophogeal adenocarcinoma in a mammal comprising administering to the mammal an effective amount of a compound of formula:
- wherein each R2′, R3′ and R5′ are independently hydrogen, optionally substituted phosphate or phosphonate;
- acyl;
- alkyl;
- amide;
- sulfonate ester;
- sulfonyl, methanesulfonyl, benzylsulfonyl, arylsulfonyl, wherein the phenyl group is optionally substituted with one or more substituents;
- a lipid;
- a phospholipid;
- an amino acid;
- a carbohydrate;
- a peptide;
- or cholesterol;
- or other pharmaceutically acceptable leaving group that, in vivo, provides a compound wherein R2′, R3′ or R5′ is independently H or mono-, di- or tri-phosphate;
- wherein Rx and Ry are independently hydrogen, optionally substituted phosphate;
- acyl;
- amide, alkyl;
- aromatic, polyoxyalkylene;
- polyethyleneglycol, optionally substituted arylsulfonyl;
- a lipid;
- a phospholipid;
- an amino acid;
- a carbohydrate;
- a peptide;
- or cholesterol;
- or other pharmaceutically acceptable leaving group;
- wherein R1 and R2 each are independently H, optionally substituted straight chained, branched or cyclic alkyl, alkenyl, or alkynyl, CO-alkyl, CO-alkenyl, CO-alkynyl, CO-aryl or heteroaryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, sulfonyl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl;
- wherein the compound is administered one time per week via intravenous infusion for three weeks followed by a one week period wherein the compound is not administered.
A method of treating esophogeal adenocarcinoma in a mammal comprising administering to the mammal a dose of 10 mg/m2 or less of a compound of the formula:
- wherein each R2′, R3′ and R5′ are independently hydrogen, optionally substituted phosphate or phosphonate;
- acyl;
- alkyl;
- amide;
- sulfonate ester;
- sulfonyl, methanesulfonyl, benzylsulfonyl, arylsulfonyl, wherein the phenyl group is optionally substituted with one or more substituents;
- a lipid;
- a phospholipid;
- an amino acid;
- a carbohydrate;
- a peptide;
- or cholesterol;
- or other pharmaceutically acceptable leaving group that, in vivo, provides a compound wherein R2′, R3′ or R5′ is independently H or mono-, di- or tri-phosphate;
- wherein Rx and Ry are independently hydrogen, optionally substituted phosphate;
- acyl;
- amide, alkyl;
- aromatic, polyoxyalkylene such as polyethyleneglycol, optionally substituted arylsulfonyl;
- a lipid;
- a phospholipid;
- an amino acid;
- a carbohydrate;
- a peptide;
- or cholesterol;
- or other pharmaceutically acceptable leaving group;
- wherein R1 and R2 each are independently H, optionally substituted straight chained, branched or cyclic alkyl, alkenyl, or alkynyl, CO-alkyl, CO-alkenyl, CO-alkynyl, CO-aryl or heteroaryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, sulfonyl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl;
- wherein the compound is administered one time per week.
Dependencies are inferred from the claim text.