Defactinib (1073154-85-4) is a potent inhibitor of FAK (IC50 = 0.6nM) and Pyk2 (IC50 = 0.6nM).1 It is active in vivo (EC50 = 26nM). FAK inhibition prevents tumor invasion and dissemination rather than tumor size reduction. Defactinib has been shown to preferentially target cancer stem cells in a mouse xenograft model of triple negative breast cancer.2 It is in multiple clinical trials for various cancers3 and it shows synergistic activity when used in combination with checkpoint immunotherapy 4-6.
1) Jones et al. (2015), A phase I study of VS-6063, a second-generation focal adhesion kinase inhibitor, in patients with advanced solid tumors; Invest. New Drugs 33 1100
2) Kolev et al. (2017), Inhibition of FAK kinase activity preferentially targets cancer stem cells; Oncotarget 8 51733
3) Marcucci et al. (2016), Anti-Cancer Stem-like Cell Compounds in Clinical Development – An Overview and Critical Appraisal; Front. Oncol. 6 115
4) Ring et al. (2015), FAK/PYK2 inhibitors defactinib and VS-4718 enhance immune checkpoint inhibitor efficacy; J. Immunother. Cancer 3 354
6) Jiang et al. (2016), Targeting Focal Adhesion Kinase Renders Pancreatic Cancers Responsive to Checkpoint Immunotherapy; Nat. Med. 22 851