Arizona Board of Regents on Behalf of University of Arizona;Board of Regents, The University of Texas System
发明人:
Emmanuelle J. Meuillet,Shuxing Zhang,Lu Chen
申请号：
US15516664
公开号：
US10448637B2
申请日:
2015.10.05
申请国别(地区):
US
年份:
2019
代理人:
摘要：
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 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.
