Astrazeneca AB has synthesized proteolysis targeting chimera (PROTAC) compounds comprising a protein cereblon (CRBN) binding moiety covalently linked to an estrogen receptor α (ER-α)-targeting moiety through a linker reported to be useful for the treatment of breast cancer.
Researchers at Shanghai Haiyan Pharmaceutical Technology Co. Ltd. and Yangtze River Pharmaceutical Group have disclosed proteolysis targeting chimeras (PROTACs) comprising an E3 ubiquitin ligase-binding moiety coupled to a polycomb protein EED-targeting moiety through linkers; they are reported to be useful for the treatment of cancer.
Researchers from the National Cancer Institute and their collaborators have presented data regarding a MLK3-degrading PROTAC, CEP1347-VHL-02, for treating triple-negative breast cancer.
Evopoint Biosciences Co. Ltd. has disclosed proteolysis targeting chimeras (PROTACs) comprising an E3 ubiquitin ligase binding moiety coupled to an Aurora kinase A (AURKA; ARK1)-targeting moiety through a linker potentially useful for the treatment of cancer.
Betta Pharmaceuticals Co. Ltd. has described proteolysis targeting chimera (PROTAC) compounds comprising a VHL-binding agent coupled to a GTPase KRAS-targeting moiety through a linker acting as KRAS degradation inducers reported to be useful for the treatment of cancer.
Treeline Biosciences Inc. has divulged proteolysis targeting chimeras (PROTACs) comprising cereblon (CRBN) ligands coupled to a Bcl-2-like protein 1 (Bcl-xl; Bcl-X; BCL2L1) targeting moiety via a linker acting as Bcl-xl degradation inducers reported to be useful for the treatment of cancer.
Bristol Myers Squibb Co. has disclosed proteolysis targeting chimera (PROTAC) compounds comprising a cereblon (CRBN) E3 ubiquitin ligase-binding moiety covalently bonded to a B-cell lymphoma 6 protein (BCL-6)-targeting moiety through a linker. They are reported to be useful for the treatment of cancer and autoimmune diseases.
Shenzhen Zhongge Biotechnology Co. Ltd. has described proteolysis targeting chimera (PROTAC) compounds comprising an E3 ubiquitin ligase binding agent coupled to interleukin-1 receptor-associated kinase 4 (IRAK-4) targeting moiety via linkers acting as IRAK-4 degradation inducers reported to be useful for the treatment of cancer, autoimmune disease, inflammatory disorders, transplant rejection, thromboembolism, atherosclerosis, myocardial infarction and metabolic syndrome.
Targeted protein degradation has yet to notch its first approval. But with more than two dozen agents now in clinical trials, the strategy’s ultimate clinical validation appears to be a matter of time.
Summit Therapeutics Inc. has identified proteolysis targeting chimera (PROTAC) compounds comprising an E3 ubiquitin ligase binding moiety coupled to a GTPase KRAS (G12D) targeting moiety through a linker acting as KRAS (G12D) inhibitors and degradation inducers reported to be useful for the treatment of cancer.
