Peptidomimetic inhibitors of STAT activity and uses thereof
AssigneesUniversity of South Florida, Yale University
InventorsJames Turkson, Richard Jove, Said M. Sebti, Andrew D. Hamilton
Life of this patent
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Abstract
The subject invention concerns compositions and methods for blocking cancer cell growth or proliferation and/or inducing cancer cell death. Compositions of the present invention are peptidomimetics that inhibit STAT function. Peptidomimetics of the invention include compounds of the formula RY*L (where Y* represents phosphotyrosine), with the R group at the Y-1 position. Peptidomimetics of the invention disrupt Stat3 activation and function. Peptidomimetics of the invention significantly inhibit tumor cell growth and induce tumor cell death.
Claims17
A method for inhibiting growth or replication, or inducing apoptosis in a target cell having aberrant or constitutive expression of Stat3, said method comprising contacting the target cell with a composition comprising a peptidomimetic having the structure shown in formula I:
- wherein
- R1 is selected from the group consisting of alkoxy, cycloalkyl, cycloalkoxy, aryl, aryloxy, alkylcarbonyl, alkoxycarbonyl, cycloalkylcarbonyl, heteroalkyl, heterocycloalkylcarbonyl, heteroaryl, arylcarbonyl, heteroarylcarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, heterocycloalkoxy, or heterocycloalkoxycarbonyl, any of which can be optionally substituted with one or more of the following:
- any halogen, —CN, —COOH, ═O, —OH, —NO2, —NH2, —N-alkyl, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryl, aryloxy, alkylcarbonyl, alkoxycarbonyl, cycloalkylcarbonyl, heteroalkyl, heterocycloalkyl, heterocycloalkylcarbonyl, heteroaryl, arylcarbonyl, heteroarylcarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, heterocycloalkoxy, and heterocycloalkoxycarbonyl;
- or a salt thereof.
A method for inhibiting growth or replication, or inducing apoptosis in a target cell having aberrant or constitutive expression of Stat3, said method comprising contacting the target cell with a composition comprising a peptidomimetic having the formula:
- R1Y*L
- wherein
- R1 is selected from the group consisting of alkoxy, cycloalkyl, cycloalkoxy, aryl, aryloxy, alkylcarbonyl, alkoxycarbonyl, cycloalkylcarbonyl, heteroalkyl, heterocycloalkylcarbonyl, heteroaryl, arylcarbonyl, heteroarylcarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, heterocycloalkoxy, or heterocycloalkoxycarbonyl, any of which can be optionally substituted with one or more of the following:
- any halogen, —CN, —COOH, ═O, —OH, —NO2, —NH2, —N-alkyl, alkyl, alkoxy, cycloalkyl, cycloalkoxy, aryl, aryloxy, alkylcarbonyl, alkoxycarbonyl, cycloalkylcarbonyl, heteroalkyl, heterocycloalkyl, heterocycloalkylcarbonyl, heteroaryl, arylcarbonyl, heteroarylcarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, heterocycloalkoxy, and heterocycloalkoxycarbonyl;
- Y* is phosphotyrosine;
- L is leucine, or another non-polar amino acid;
- or a salt thereof.
Dependencies are inferred from the claim text.