Structural requirements for STAT3 binding and recruitment to phosphotyrosine ligands
AssigneeBaylor College of Medicine
InventorDavid Tweardy
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Abstract
Inhibitors of Stat3 are disclosed, including small molecules and peptide mimetic inhibitors. Specific Stat3 inhibitors of the invention are useful as beta-turn mimetics. Also disclosed are pharmaceutical compositions of the Stat3 inhibitors of the invention, and methods for using the compounds of the invention to inhibit growth of a cell or to inhibit protein-protein interactions modulated by SH2 domains. Methods of screening for Stat3 inhibitors are also provided.
Claims29
A Stat3 inhibitor comprising a beta-turn mimetic wherein said beta-turn mimetic is capable of binding to a sequence located within the SH2 domain of Stat3.
The Stat3 inhibitor of claim 20, wherein binding the sequence within the SH2 domain further comprises interaction with residues K589, R607, or both.
A method of inhibiting Stat3 in at least one cell of an individual, comprising administering to the individual a composition of FIG. 10, FIG. 11, or a mixture thereof.
A method of treating cancer in an individual, comprising administering to the individual a composition of FIG. 10, FIG. 11, or a mixture thereof.
A composition dispersed in a pharmaceutically acceptable carrier and comprising a a composition of FIG. 10, FIG. 11, or a mixture thereof.
A method of screening for an inhibitor of Stat3, comprising:
- providing a Stat3 SH2 domain, wherein said domain is capable of binding to a beta turn in a Stat3-interacting molecule;
- providing a test compound;
- and
- assaying binding of said test compound to said SH2 domain, wherein when said test compound binds said SH2 domain, said test compound is said inhibitor.
Dependencies are inferred from the claim text.