US 9655914 B2 - Compositions Including Triciribine And Epidermal Growth Factor Receptor Inhibitor Compounds Or Salts Thereof And Methods Of Use Thereof - The Lens - Free & Open Patent and Scholarly Search

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US 9655914 B2

Compositions Including Triciribine And Epidermal Growth Factor Receptor Inhibitor Compounds Or Salts Thereof And Methods Of Use Thereof

Published: May 23, 2017
Earliest Priority: Mar 29 2004
Family: 9
Cited Works: 401
Cited by: 0
Cites: 76
Sequences: 6
Additional Info: Cited Works Full text Published Sequence

Abstract

This application relates to combination therapies including triciribine compounds and epidermal growth factor receptor inhibitor compounds, particularly erlotinib-like compounds and compositions with reduced toxicity for the treatment and prevention of tumors, cancer, and other disorders associated with abnormal cell proliferation.

Claims

A method for treating a subject having a tumor or cancer, which tumor or cancer overexpresses AKT kinase comprising:
a. administering to said subject:
i. at least one compound of formula I selected from the group consisting of the following compounds:

wherein each R₂′, R₃′, and R₅′ is independently hydrogen; optionally substituted phosphate or phosphonate; mono-, di-, or triphosphate; acyl; lower acyl; alkyl; lower alkyl; amide; sulfonate ester; alkyl sulfonate ester; arylalkyl sulfonate ester; sulfonyl; methanesulfonyl; benzyl sulfonyl, wherein the phenyl group of said benzyl is optionally substituted with one or more halo, hydroxyl, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate, or phosphonate; optionally substituted arylsulfonyl; a lipid; phospholipid; an amino acid; a carbohydrate; a peptide; or cholesterol; or other pharmaceutically acceptable leaving group that, in vivo, provides a compound of said formula I wherein R₂′, R₃′ or R₅′ is independently H or mono-, di- or tri-phosphate;

wherein R^xand R^yare independently hydrogen; optionally substituted phosphate; acyl; lower acyl; amide; alkyl; lower 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; and

wherein R₁and R₂each are independently H, optionally substituted straight chained, branched or cyclic alkyl, lower alkyl, alkenyl, or alkynyl, CO-alkyl, CO-alkenyl, CO-alkynyl, CO-aryl or heteroaryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, sulfonyl, alkylsulfonyl, arylsulfonyl, or aralkylsulfonyl;
ii. one or more epidermal growth factor receptor inhibitors or a salt thereof; and

iii. a pharmaceutically acceptable carrier,

wherein the amount of compound of formula I administered to said subject is at least 2 mg/m².
The method of claim 1, wherein the compound of formula I is triciribine.
The method of claim 1, wherein the compound of formula I is triciribine phosphate.
The method of claim 1, wherein the compound of formula I is triciribine phosphonate.
The method of claim 1, wherein the compound of formula I is present in a dose amount of at least 20 mg/m².
The method of claim 1, wherein the compound of formula I is present in an amount of at least 10 mg/m².
The method of claim 1, wherein the administration is parenteral administration.
The method of claim 7, wherein the parenteral administration is intravenous administration.
The method of claim 1, wherein the administration is oral administration.
The method of claim 1, suitable for intravenous administration.
The method of claim 1, wherein the epidermal growth factor receptor inhibitor compound or salt thereof is present in a dose about 0.1 mg/m²to about 200 mg/m².
The method of claim 1, wherein the epidermal growth factor receptor inhibitor compound or salt thereof is present in a dose about 1 mg/m²to about 150 mg/m².
The method of claim 1, wherein the epidermal growth factor receptor inhibitor compound or salt thereof is present in a dose about 10 mg/m²to about 100 mg/m².
The method of claim 1, wherein the epidermal growth factor receptor inhibitor compound or salt thereof is present in a dose about 25 mg/m²to about 50 mg/m².
The method of claim 1, wherein the administration of a compound of formula I and epidermal growth factor receptor inhibitor compound or salt thereof is concurrently administered.
The method of claim 1, wherein the administration of a compound of formula I is followed by the administration of epidermal growth factor receptor inhibitor compound or salt thereof.
The method of claim 1, wherein the administration of epidermal growth factor receptor inhibitor compound or salt thereof is followed by the administration of a compound of formula I.
The method of claim 1, wherein the epidermal growth factor receptor inhibitor is gefitinib.
The method of claim 1, wherein the epidermal growth factor receptor inhibitor is erlotinib.

Owners (US)

University Of South Florida (Jun 08 2015)
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Applicants

Univ South Florida
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Inventors

Cheng Jin Q
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Sebti Said M
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CPC Classifications

A61K31/7064
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A61K9/0019
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A61K9/0053
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A61K31/517
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A61K31/5377
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A61K31/7068
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A61K31/7076
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A61K45/06
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C12Q1/6886
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C12Q2600/106
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C12Q2600/158
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G01N33/57426
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G01N2333/912
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IPC Classifications

A61K31/70
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A61K9/00
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A61K31/517
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A61K31/5377
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A61K31/7052
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A61K31/7064
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A61K31/7076
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A61K45/06
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Document History

Publication: May 23, 2017
US 9655914 B2
Application: Dec 28, 2015
US 201514998352 A
Priority: Dec 28, 2015
US 201514998352 A
Priority: Nov 27, 2013
US 201314092323 A
Priority: Apr 23, 2012
US 201213453789 A
Priority: May 12, 2008
US 11886108 A
Priority: Mar 29, 2005
US 9608205 A
Priority: Mar 29, 2004
US 55759904 P

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