ArticleScientific reports2019
Small molecule FAK activator promotes human intestinal epithelial monolayer wound closure and mouse ulcer healing.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 37 citations in OpenAlex.
- A self-crosslinkable, adhesive intestine-derived extracellular matrix hydrogel enhances organoid retention and restores intestinal barrier integrity.Bioactive materials · 2027Article
- Balsa Wood-Loaded Polyvinyl Alcohol/Chitosan/Zinc Gluconate Hydrogel Applied as Wound Dressing.Polymers · 2026Article
- From disease model to therapeutic insight: An engineered hydrogel reveals the role of matrix viscous dissipation in intervertebral disc degeneration.Bioactive materials · 2026Article
- Activation of the FAK-MAPK/ERK1 pathway promotes intestinal epithelial cell sheet migration during fistula tract repair.Scientific reports · 2026Article
- CD98hc controls CNS angiogenesis and blood-brain barrier integrity through localized regulation of the systemic integrin-FAK pathway.Nature cardiovascular research · 2026Article
- Discovery of Focal Adhesion Kinase (FAK) activators to promote intestinal mucosal healing.European journal of medicinal chemistry · 2026Article
- Article
- Focal adhesion kinase: A promising regulator of colitis-associated healing.World journal of gastroenterology · 2025Review
- M64HCl, a focal adhesion kinase activator, promotes intestinal mucosal healing in rats.BMC gastroenterology · 2025Article
- Focal Adhesion Kinase and Colony Stimulating Factors: Intestinal Homeostasis and Innate Immunity Crosstalk.Cells · 2024Review
- Protective effect ofFrontiers in medicine · 2024Article
- Enhanced Bone Regeneration through Regulation of Mechanoresponsive FAK-ERK1/2 Signaling by ZINC40099027 during Distraction Osteogenesis.International journal of medical sciences · 2024Article
- Restore Intestinal Barrier Integrity: An Approach for Inflammatory Bowel Disease Therapy.Journal of inflammation research · 2024Review
- Sustained intestinal epithelial monolayer wound closure after transient application of a FAK-activating small molecule.PloS one · 2024Article
- The dysadherin/FAK axis promotes individual cell migration in colon cancer.International journal of biological sciences · 2024Article
- On the Value of In Vitro Cell Systems for Mechanobiology from the Perspective of Yes-Associated Protein/Transcriptional Co-Activator with a PDZ-Binding Motif and Focal Adhesion Kinase and Their Involvement in Wound Healing, Cancer, Aging, and Senescence.International journal of molecular sciences · 2023Review
- The Integrin Pathway Partially Mediates Stretch-Induced Deficits in Primary Rat Microglia.Molecular neurobiology · 2023Article
- An αvβ3 integrin checkpoint is critical for efficient TNature immunology · 2023Article
- A novel drug-like water-soluble small molecule Focal Adhesion Kinase (FAK) activator promotes intestinal mucosal healing.Current research in pharmacology and drug discovery · 2023Article
- Flow-Induced Secretion of Endothelial Heparanase Regulates Cardiac Lipoprotein Lipase and Changes Following Diabetes.Journal of the American Heart Association · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
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 Pyk2-Tyr-402 or Src-Tyr-419. ZINC40099027 did not stimulate proliferation, and stimulated wound closure independently of proliferation. The FAK inhibitor PF-573228 prevented ZINC40099027-stimulated wound closure. In both mouse ulcer models, ZINC40099027accelerated mucosal wound healing. FAK phosphorylation was increased in jejunal epithelium at the ulcer edge, and Ki-67 staining was unchanged in jejunal mucosa. ZINC40099027 serum concentration at sacrifice resembled the effective concentration in vitro. Weight, creatinine and ALT did not differ between groups. Small molecule FAK activators can specifically promote epithelial restitution and mucosal healing and may be useful to treat gut mucosal injury.
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