Animal Health – Loren D. Walensky, Ruben Carrasco, Gregory H. Bird, Dana Farber Cancer Institute Inc

Abstract for “Targeting cancer deregulated wnt signaling using stabilized alpha helices of the bcl-9”

“The invention provides structurally-constrained peptides by hydrocarbon stapling of a BCL9 HD2 helix for use as a therapeutic agent. The invention further provides methods and kits for use of the structurally-constrained peptide of the instant invention. This invention is based at least partially on the following results: Hydrocarbon stapled helical proteins exhibit excellent proteolytic and acid stability, restore the native structure of the protein, and have superior pharmacokinetic characteristics compared to unmodified peptides. They also disrupt the BCL-9/??-catenin interaction and interfere with Wnt/??-catenin signaling to provide therapeutic benefit in a variety human diseases, including cancer.

Background for “Targeting cancer deregulated wnt signaling using stabilized alpha helices of the bcl-9”

“Hydrocarbon Stapping of Polypeptides”

“SAH-BCL9 Peptides”

“Mutations and Truncations and Extensions of HD2 Domain & BCL9 Peptides

“Stabilization HD2 Domain and BCL9 Peptides

“Synthesis Of Peptides”

“Definitions”

“Pharmaceutical Compositions & Routes of Administration”

“Kits”

“EXAMPLES”

“Example 1. “Example 1.

“Example 2. “Example 2. Protein Production and Purification

“Example 3. “Example 3. GST Pull-Down Assays

“Example 4. “Example 4.” Patient Samples and Cell Lines

“Example 6. “Example 6.

“Example 7. Histopathological Analysis and Immunohistochemistry”

“Example 8. “Example 8. Quantitative reverse transcription-PCR”

“Example 9. Gene Expression Profiling”

“Example 10. “Example 10. Cell Proliferation, Viability assay and Detection Of Apoptosis”

“Example 11. “Example 11.

“Example 12. “Example 12.” In Vivo Anti-Tumor Activity of SAH-BCL9B in Vivo (Xenograft Modells)”

“Example 13. “Example 13.

“Example 14. VEGF ELISA

“Example 16. VEGF Promoter Luciferase Assays”

“Example 17. Lentiviral Vectors

“Example 18. Lentivirus Production & Infection

“Example 19. “Example 19. Establishment of Single-Cell Cultures”

“Example 20. Chromatin Immunoprecipitation”

“Example 21. Reporter Assays”

“Example 22. SAH-BCL9B: Selective Dissociation from the BCL9/?Catenin Complex

“Example 23. “Example 23.

“Example 24. Combination Therapies

“INCORPORATION BY RESEARCH”

“EQUIVALENTS”

Summary for “Targeting cancer deregulated wnt signaling using stabilized alpha helices of the bcl-9”

“Hydrocarbon Stapping of Polypeptides”

“SAH-BCL9 Peptides”

“Mutations and Truncations and Extensions of HD2 Domain & BCL9 Peptides

“Stabilization HD2 Domain and BCL9 Peptides

“Synthesis Of Peptides”

“Definitions”

“Pharmaceutical Compositions & Routes of Administration”

“Kits”

“EXAMPLES”

“Example 1. “Example 1.

“Example 2. “Example 2. Protein Production and Purification

“Example 3. “Example 3. GST Pull-Down Assays

“Example 4. “Example 4.” Patient Samples and Cell Lines

“Example 6. “Example 6.

“Example 7. Histopathological Analysis and Immunohistochemistry”

“Example 8. “Example 8. Quantitative reverse transcription-PCR”

“Example 9. Gene Expression Profiling”

“Example 10. “Example 10. Cell Proliferation, Viability assay and Detection Of Apoptosis”

“Example 11. “Example 11.

“Example 12. “Example 12.” In Vivo Anti-Tumor Activity of SAH-BCL9B in Vivo (Xenograft Modells)”

“Example 13. “Example 13.

“Example 14. VEGF ELISA

“Example 16. VEGF Promoter Luciferase Assays”

“Example 17. Lentiviral Vectors

“Example 18. Lentivirus Production & Infection

“Example 19. “Example 19. Establishment of Single-Cell Cultures”

“Example 20. Chromatin Immunoprecipitation”

“Example 21. Reporter Assays”

“Example 22. SAH-BCL9B: Selective Dissociation from the BCL9/?Catenin Complex

“Example 23. “Example 23.

“Example 24. Combination Therapies

“INCORPORATION BY RESEARCH”

“EQUIVALENTS”

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