H. Lee Moffitt Cancer Center and Research Institute, Inc.

University of South Florida

Haitao Ji

Alan F List

Jianfeng Cai

Yan Shi

Peng Sang

Min Zhang

Disclosed herein is a series of helical sulfono-γ-AApeptides that mimic the binding mode of the α-helical HD2 domain of B-Cell Lymphoma 9 (BCL9). As disclosed herein, sulfono-γ-AApeptides can structurally and functionally mimic the α-helical domain of BCL9, and selectively disrupt β-catenin/BCL9 PPIs with even higher potency. More intriguingly, these sulfono-γ-AApeptides can enter cancer cells, bind with β-catenin and disrupt β-catenin/BCL PPI, and exhibit excellent cellular activity, which is much more potent than the BCL9 peptide. Furthermore, enzymatic stability studies demonstrated the remarkable stability of the helical sulfono-γ-AApeptides, with no degradation in the presence of pronase for 24 h, augmenting their biological potential.

B-catenin/B-cell Lymphoma 9 protein-protein interaction inhibiting peptidomimetics

Disclosed herein are small molecule pyrin-domain targeted NLRP3 inflammasome inhibitors.

Small molecule pyrin-domain targeted NLRP3 inflammasome inhibitors

Disclosed are inhibitors for the β-catenin/T-cell factor interaction. The inhibitors are selective for β-catenin/T-cell factor over β-catenin/phosphocadherin, and β-catenin/phosphoAPC interactions. Methods of using the disclosed compounds to treat cancer are also disclosed.

Peptidomimetic inhibitors of β-catenin/Tcf protein-protein interaction

Disclosed are inhibitors for the β-catenin/BCL9 interaction. The inhibitors are selective for β-catenin/BCL9 over β-catenin/cadherin interactions. Methods of using the disclosed compounds to treat cancer are also disclosed.

β-catenin and B-cell lymphoma 9 (BCL9) inhibitors

Peptides useful as inflammasome inhibitors are disclosed and can comprise an H2 helix of a pyrin domain, wherein at least two non-consecutive amino acids of the H2 helix are covalently linked. Methods of treating a subject with a disease comprising administering to the subject the disclosed peptides are also disclosed. Further, disclosed herein are methods of inhibiting binding between a first polypeptide comprising a pyrin domain and a second polypeptide comprising a pyrin domain, the method comprising contacting either the first polypeptide or the second polypeptide with the disclosed peptides.

Stapled H2 pyrin peptides

Disclosed are inhibitors for the β-catenin/BCL9 interaction. The inhibitors are selective for β-catenin/BCL9 over β-catenin/cadhenin interactions. Methods of using the disclosed compounds to treat cancer are also disclosed.

Inhibitors for the B-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction

Disclosed are inhibitors for the &#x3b2;-catenin/BCL9 interaction. The inhibitors are selective for &#x3b2;-catenin/BCL9 over &#x3b2;-catenin/cadherin interactions. Methods of using the disclosed compounds to treat cancer are also disclosed.

Disclosed are inhibitors for the &#x3b2;-catenin/T-cell factor interaction. The inhibitors are selective for &#x3b2;-catenin/T-cell factor over &#x3b2;-catenin/cadherin and &#x3b2;-catenin/APC interactions. Methods of using the disclosed compounds to treat cancer are also disclosed.

Growing community of inventors

Tampa, FL, United States of America

Haitao Ji