University of Texas System

The University of Arizona

Shuxing Zhang

Emmanuelle J Meuillet

Garth Powis

Daruka Mahadevan

Eugene A Mash

Vijay Gokhale

Lu Chen

Kapil Mehta

Jansina Fok

Sylvestor Moses

Hui-Kuan Lin

Chia-Hsin Chan

John Kenneth Morrow

Anupam Kumar

Vijay M Gohkale

Vijay M Gokhale

Identification and evaluation of a set of first-in-class potent inhibitors targeting a new cancer target, Grb2-associated binder-1 (GAB1), which integrates signals from different signaling pathways and is frequently over-expressed in cancer cells. Intensive computational modeling is utilized to understand the structure of the GAB1 pleckstrin homology (PH) domain and screened five million compounds. Upon biological evaluation, several inhibitors were found that induced large conformational changes of the target structure exhibited strong selective binding to GAB1 PH domain. Particularly, these inhibitors demonstrated potent and tumor-specific cytotoxicity in breast cancer cells. This targeting GAB1 signaling may be used for cancer therapy, especially for triple negative breast cancer patients.

Inhibitors of GRB2-associated binding protein 1 (GAB1) and methods of treating cancer using the same

Identification and evaluation of a set of first-in-class potent inhibitors targeting a new cancer target, Grb2-associated binder&#x2dc;1 (GAB1), which integrates signals from different signaling pathways and is frequently over-expressed in cancer ceils. Intensive computational modeling is utilized to understand the structure of the GAB1 pleckstrin homology (PH) domain and screened five million compounds. Upon biological evaluation, several inhibitors were found that induced large conformational changes of the target structure exhibited strong selective binding to GAB1 PH domain. Particularly, these inhibitors demonstrated potent and tumor-specific cytotoxicity in breast cancer cells. This targeting GAB1 signaling may be used for cancer therapy, especially for triple negative breast cancer patients.

T-lymphocyte invasion and metastases (Tiam-1) has been identified as a marker and anti-cancer drug target for therapy of metastatic bone cancer in individuals afflicted with prostate cancer. The present disclosure provides methods and compounds for inhibiting metastases by disrupting Tiam-1 expression and activity. One particularly preferred compound comprises a disulfomanide of the formula.

Treatment and/or prevention of bone metastasis

Provided are methods and compositions for the treatment of diseases such as cancer. In certain aspects, compounds which can inhibit Skp2 are provided. Specifically chromenone derivatives are disclosed that have the capability toward reducing differentiation of pluripotent, multipotent or totipotent cells and thus have therapeutic utility in the treatment of a proliferative disease such as cancer.

Anti-cancer compounds

Pleckstrin homology domain binding compounds, pharmaceutical compositions including such compounds, and methods for their use are described herein.

Small molecule inhibitors of the pleckstrin homology domain and methods for using same

Methods and compounds for treating cancer, dmg resistance and/or metastasis are described herein. These methods and compounds can inhibit the expression of aberrant TG2 expression and/or inhibit the binding of GTP to TG2, and thereby prevent the induction of epithelial to mesenchymal transition of cancer cells, and a stem cell-like phenotype.

TG2 inhibitors and uses thereof

Pleckstrin homology domain binding compounds, pharmaceutical compositions including such compounds, and methods for their use are described herein. 

Growing community of inventors

Pearland, TX, United States of America

Shuxing Zhang