Discovery of Novel Small-Molecule FAK Activators Promoting Mucosal Healing

Qinggang Wang; Ricardo Gallardo-Macias; Rashmi; Mikhail Y. Golovko; Ahmed Adham Raafat Elsayed; Shyam K. More; Sema Oncel; Vadim J. Gurvich; Marc D. Basson

doi:10.1021/acsmedchemlett.0c00311

Discovery of Novel Small-Molecule FAK Activators Promoting Mucosal Healing

Qinggang Wang, Ricardo Gallardo-Macias, Rashmi, Mikhail Y. Golovko, Ahmed Adham Raafat Elsayed, Shyam K. More, Sema Oncel, Vadim J. Gurvich, Marc D. Basson

Institute for Therapeutics Discovery and Development

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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.

Original language	English (US)
Pages (from-to)	356-364
Number of pages	9
Journal	ACS Medicinal Chemistry Letters
Volume	12
Issue number	3
DOIs	https://doi.org/10.1021/acsmedchemlett.0c00311
State	Published - Mar 11 2021

Bibliographical note

Funding Information:
This work was supported in part by NIH Grant U54GM128729 (M.D.B. and M.Y.G.). We also thank UND for a postdoctoral fellowship to Rashmi and Svetlana Golovko, Phar.D., MS research specialist, for her contribution to the MS analysis.

Publisher Copyright:
© 2021 American Chemical Society.

Keywords

Focal adhesion kinase
medicinal chemistry
migration
mucosal healing
restitution

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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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AU - More, Shyam K.

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AU - Gurvich, Vadim J.

AU - Basson, Marc D.

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Discovery of Novel Small-Molecule FAK Activators Promoting Mucosal Healing

Abstract

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