NU2022-106
INVENTORS
Gary Schiltz*
Daniela Matei*
BACKGROUND
Proteolysis-targeting chimeric molecules (PROTACs) are an emergent form of technology that may be utilized to target previously “undruggable” targets, transcription factors, and non-enzymatic proteins related to disease. Despite the increased use of PROTACs to leverage E3 ligases for total protein degradation, there is still a need for novel PROTACs capable of degrading proteins, particularly multi-functional proteins such as those involved in cancer. Northwestern researchers have developed PROTACs that induce degradation of tissue transglutaminase 2 (TG2). TG2 is a multi-functional enzyme that functions as a tumor promoter in multiple cancer types including ovarian, pancreatic, lung, breast cancer, and glioblastoma. The PROTACs are comprised of a moiety that binds to TG2, a moiety that binds to an E3 ubiquitin ligase, and a linker that covalently bonds the moieties together. In initial in vitro studies, TG2 PROTACs induced degradation of TG2 in ovarian cancer cell lines treated with the compounds. Additionally, experimental evidence showed reduced migration of cells following degradation of TG2. Together, these novel compounds provide a potential therapeutic for total protein degradation and treatment of TG2 related cancers and other diseases.
IP STATUS
A non-provisional patent has been filed.