Therapeutic small molecule degrader of FAK and PYK2 Selective PROTAC degraders of FAK and PYK2. Focal Adhesion Kinase (FAK) and Proline-Rich Tyrosine Kinase 2 (PYK2) are non-receptor tyrosine kinases that act downstream of integrins and focal adhesion complexes, linking extracellular matrix signals to intracellular signaling pathways that control cell adhesion, migration, and survival. These kinases are overexpressed and critical in many cancers and other disorders. Despite several FAK inhibitors advancing to clinical evaluation, strategies to target the activities of FAK and PYK2 kinases have failed to show meaningful efficacy as single agents. Dr. Behnam Nabet’s group at Fred Hutchinson Cancer Center has developed a set of novel proteolysis targeting chimera (PROTAC) molecules that can selectively and rapidly degrade FAK and PYK2. These small molecules have the potential to be developed as therapeutics for a variety of solid tumors, inflammatory and fibrotic diseases. <ul> <li>Cancer: Pancreatic, cervical, breast, mesothelioma, NSCLC, glioblastoma</li> <li>Fibrosis: Liver, cardiac and renal fibrosis</li> <li>Inflammation: Asthma, arthritis, IBD</li> </ul> <ul> <li>Selective, rapid degradation of target proteins</li> <li>Leverages E3 ligase-mediated ubiquitination to target disease-causing proteins</li> </ul> <ul> <li>Behnam Nabet, PhD - Assistant Professor, Human Biology Division</li> </ul> Preclinical in vitro Provisional Patent Application Filed 23227NabetPYK2tpd.pdf FAK |PYK2 | degrader | pancreatic cancer | breast cancer | Behnam Nabet | small molecule | Mesothelioma | NSCLC | Fibrosis | Autoimmune Haffner-prac1-prostate-cancer