FAK inhibitors as promising anticancer targets: present and future directions

Muhamad Mustafa; Amer Ali Abd El-Hafeez; Dalia A Abdelhafeez; Dalia Abdelhamid; Yaser A Mostafa; Pradipta Ghosh; Alaa M Hayallah; Gamal El-Din A Abuo-Rahma

doi:10.4155/fmc-2021-0015

FAK inhibitors as promising anticancer targets: present and future directions

Future Med Chem. 2021 Sep;13(18):1559-1590. doi: 10.4155/fmc-2021-0015. Epub 2021 Aug 3.

Authors

Muhamad Mustafa^{1

2}, Amer Ali Abd El-Hafeez^{3

4}, Dalia A Abdelhafeez⁵, Dalia Abdelhamid¹, Yaser A Mostafa⁶, Pradipta Ghosh^{4

7

8

9}, Alaa M Hayallah^{2

6

10}, Gamal El-Din A Abuo-Rahma^{1

2}

Affiliations

¹ Department of Medicinal Chemistry, Minia University, Minia, 61519, Egypt.
² Pharmaceutical Chemistry Department, Deraya University, Minia, 61111, Egypt.
³ Pharmacology & Experimental Oncology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt.
⁴ Department of Cellular & Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
⁵ Department of Pathology, Minia University, Egypt.
⁶ Pharmaceutical Organic Chemistry Department, Assiut University, 71526, Egypt.
⁷ Department of Medicine, University of California San Diego, La Jolla, CA, USA.
⁸ Rebecca & John Moore Comprehensive Cancer Center, University of California San Diego, La Jolla, CA, USA.
⁹ Veterans Affairs Medical Center, La Jolla, CA, USA.
¹⁰ Pharmaceutical Chemistry Department, Sphinx University, New Assiut, Egypt.

Abstract

FAK, a nonreceptor tyrosine kinase, has been recognized as a novel target class for the development of targeted anticancer agents. Overexpression of FAK is a common occurrence in several solid tumors, in which the kinase has been implicated in promoting metastases. Consequently, designing and developing potent FAK inhibitors is becoming an attractive goal, and FAK inhibitors are being recognized as a promising tool in our armamentarium for treating diverse cancers. This review comprehensively summarizes the different classes of synthetically derived compounds that have been reported as potent FAK inhibitors in the last three decades. Finally, the future of FAK-targeting smart drugs that are designed to slow down the emergence of drug resistance is discussed.

Keywords: FAK inhibitors; PROTACs; cancer; focal adhesion kinase.

Publication types

Research Support, N.I.H., Extramural
Review

MeSH terms

Amino Acid Sequence
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology
Binding Sites
Biomarkers, Tumor / antagonists & inhibitors*
Drug Design
Focal Adhesion Kinase 1 / antagonists & inhibitors*
Heterocyclic Compounds / chemistry
Humans
Models, Molecular
Protein Binding
Protein Conformation
Protein Kinase Inhibitors / chemistry*
Protein Kinase Inhibitors / pharmacology
Signal Transduction
Structure-Activity Relationship

Substances

Antineoplastic Agents
Biomarkers, Tumor
Heterocyclic Compounds
Protein Kinase Inhibitors
Focal Adhesion Kinase 1
PTK2 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding