2. Academic Validation
  3. Drug Discovery Targeting Focal Adhesion Kinase (FAK) as a Promising Cancer Therapy

Drug Discovery Targeting Focal Adhesion Kinase (FAK) as a Promising Cancer Therapy

  • Molecules. 2021 Jul 13;26(14):4250. doi: 10.3390/molecules26144250.
Xiao-Jing Pang 1,  Xiu-Juan Liu 1,  Yuan Liu 1,  Wen-Bo Liu 1,  Yin-Ru Li 2,  Guang-Xi Yu 2,  Xin-Yi Tian 2,  Yan-Bing Zhang 1,  Jian Song 1 2,  Cheng-Yun Jin 1 2,  Sai-Yang Zhang 1 2 3 4
Affiliations

Affiliations

  • 1 Key Laboratory of Advanced Drug Preparation Technologies (Ministry of Education), Institute of Drug Discovery & Development, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
  • 2 School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.
  • 3 Henan Institute of Advanced Technology, Zhengzhou University, Zhengzhou 450001, China.
  • 4 State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210023, China.
PMID: 34299525 DOI: 10.3390/molecules26144250
Abstract

FAK is a nonreceptor intracellular tyrosine kinase which plays an important biological function. Many studies have found that FAK is overexpressed in many human Cancer cell lines, which promotes tumor cell growth by controlling cell adhesion, migration, proliferation, and survival. Therefore, targeting FAK is considered to be a promising Cancer therapy with small molecules. Many FAK inhibitors have been reported as Anticancer agents with various mechanisms. Currently, six FAK inhibitors, including GSK-2256098 (Phase I), VS-6063 (Phase II), CEP-37440 (Phase I), VS-6062 (Phase I), VS-4718 (Phase I), and BI-853520 (Phase I) are undergoing clinical trials in different phases. Up to now, there have been many novel FAK inhibitors with Anticancer activity reported by different research groups. In addition, FAK degraders have been successfully developed through "proteolysis targeting chimera" (PROTAC) technology, opening up a new way for FAK-targeted therapy. In this paper, the structure and biological function of FAK are reviewed, and we summarize the design, chemical types, and activity of FAK inhibitors according to the development of FAK drugs, which provided the reference for the discovery of new Anticancer agents.

Keywords

PROTAC; anticancer activity; diaminopyrimidines; focal adhesion kinase; triazine.

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