Focal Adhesion Kinase (FAK) is a cytoplasmic protein tyrosine kinase. It resides at the sites of integrin clustering, known as focal adhesions, responsible to attaching the cell to the extracellular matrix. PYK2 (=FAK2) is a family member of FAK, which is expressed mainly in the brain and the hematopoietic system.

FAK is over-expressed in numerous cancer types, and is used as a marker for invasion and metastasis. Deletion of FAK showed that it is essential for malignant tumor formation and progression (e.g., in breast cancer).

FAK/PYK2 inhibition also affects bone mass, as it enhances the activity of bone mineral absorbing cells, the osteoclasts.

Synergistic effect of FAK/PYK2 inhibitors with anti-angiogenesis inhibitors, such as anti-VEGF drugs, has indicated their potential as novel anti-angiogenesis agents.

Hence, a dual FAK/PYK2 inhibitor has a potential of being novel anti-proliferating agents for cancer. They may also be used as anti-angiogenic agents in combination with other anti-VEGF treatment. It has been shown that such inhibitors have a synergy effect with chemotherapy, overcoming chemo-resistance and lowering the required dose of cytotoxic agents. Finally, due to their effect on osteoclasts, such drugs hold promise for patients with myeloma bone disease (MBD) and osteoporosis.

Dynamix is developing its DNX-5000 series of otherwise selective dual FAK/PYK2 kinase inhibitors for these indications.