The University of Arizona

University of Texas System

Emmanuelle J Meuillet

Shuxing Zhang

Garth Powis

Daruka Mahadevan

Eugene A Mash

Vijay Gokhale

Lu Chen

Vijay M Gohkale

Sylvestor Moses

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

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

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

Growing community of inventors

Tucson, AZ, United States of America

Emmanuelle J Meuillet