2. Academic Validation
  3. Discovery of Novel Small-Molecule FAK Activators Promoting Mucosal Healing

Discovery of Novel Small-Molecule FAK Activators Promoting Mucosal Healing

  • ACS Med Chem Lett. 2021 Feb 16;12(3):356-364. doi: 10.1021/acsmedchemlett.0c00311.
Qinggang Wang 1,  Ricardo Gallardo-Macias 2,  Rashmi 1,  Mikhail Y Golovko 3,  Ahmed Adham Raafat Elsayed 1,  Shyam K More 1,  Sema Oncel 3,  Vadim J Gurvich 2,  Marc D Basson 1 3 4
Affiliations

Affiliations

  • 1 Department of Surgery, University of North Dakota School of Medicine and Health Sciences, 1301 North Columbia Road, Grand Forks, North Dakota 58201, United States.
  • 2 Institute for Therapeutics Discovery and Development and Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, 717 Delaware Street SE, Minneapolis, Minnesota 55414, United States.
  • 3 Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, 1301 North Columbia Road, Grand Forks, North Dakota 58201, United States.
  • 4 Department of Pathology, University of North Dakota School of Medicine and Health Sciences, 1301 North Columbia Road, Grand Forks, North Dakota 58201, United States.
PMID: 33738062 DOI: 10.1021/acsmedchemlett.0c00311
Abstract

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.

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