Small molecule FAK activator promotes human intestinal epithelial monolayer wound closure and mouse ulcer healing.

ABSTRACT: GI mucosal healing requires epithelial sheet migration. The non-receptor tyrosine kinase focal adhesion kinase (FAK) stimulates epithelial motility. A virtual screen identified the small drug-like FAK mimic ZINC40099027, which activates FAK. We assessed whether ZINC40099027 promotes FAK-Tyr-397 phosphorylation and wound healing in Caco-2 monolayers and two mouse intestinal injury models. Murine small bowel ulcers were generated by topical serosal acetic acid or subcutaneous indomethacin in C57BL/6J mice. One day later, we began treatment with ZINC40099027 or DMSO, staining the mucosa for phosphorylated FAK and Ki-67 and measuring mucosal ulcer area, serum creatinine, ALT, and body weight at day 4. ZINC40099027 (10-1000 nM) dose-dependently activated FAK phosphorylation, without activating

SUBMITTER: Wang Q 

PROVIDER: S-EPMC6789032 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature