Open AccessDiscovery of Novel Small-Molecule FAK Activators Promoting Mucosal Healing
Author(s) -
Qinggang Wang,
Ricardo GallardoMacias,
Rashmi Rashmi,
Mikhail Y. Golovko,
Ahmed Adham Raafat Elsayed,
Shyam K. More,
Sema Oncel,
Vadim J. Gurvich,
Marc D. Basson
Publication year - 2021
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.0c00311
Subject(s) - wound healing , medicine , focal adhesion , inflammatory bowel disease , necrotizing enterocolitis , tyrosine kinase , kinase , bioinformatics , phosphorylation , cancer research , pharmacology , immunology , pathology , receptor , biology , disease , microbiology and biotechnology
Gastrointestinal mucosal wounds are common to patients injured by factors as diverse as drugs, inflammatory bowel disease, peptic ulcers, and necrotizing enterocolitis. However, although many drugs are used to ameliorate injurious factors, there is no drug available to actually stimulate mucosal wound healing. Focal adhesion kinase (FAK), a nonreceptor tyrosine kinase, induces epithelial sheet migration and wound healing, making FAK a potential pharmacological target in this regard. In our previous research, we found a lead compound with drug-like properties, ZINC40099027, which promotes FAK phosphorylation, inducing mucosal healing in murine models. Herein we describe the design and optimization of a small library of novel FAK activators based on ZINC40099027 and their applications toward human intestinal epithelial wound closure and mouse ulcer healing.