Cancer

Cell culture studies identified a defactinib-based FAK degrader compound that could help treat prostate cancer and triple-negative breast cancer (TNBC). The compound consists of an analog of the FAK inhibitor defactinib linked to a hydroxyproline-based vHL ligand and targets FAK to the proteasome for degradation instead of inhibiting FAK directly. In a human prostate cancer cell-based activity assay, the compound degraded FAK with a IC₅₀ of 3 nM and decreased FAK activity compared with defactinib. In a human TNBC cell line, the compound decreased migration and invasion. Next steps could include testing the FAK degrader in animal models of the two cancers.

Pfizer Inc. and Verastem Inc. have defactinib in Phase II testing for mesothelioma and non-small cell lung cancer (NSCLC), Phase I/II testing for ovarian cancer, Phase I testing for pancreatic cancer and solid tumors and preclinical testing for breast cancer...