Astrazeneca AB has disclosed proteolysis targeting chimera (PROTAC) compounds comprising an E3 ubiquitin ligase-binding moiety coupled to an interleukin-1 receptor-associated kinase 4 (IRAK-4)-targeting moiety through a linker acting as IRAK-4 degradation inducers reported to be useful for the treatment of cancer, inflammation, autoimmune diseases and respiratory disorders.
One of the functions of tumor-associated macrophages (TAMS) is to protect the tumor against the immune system, inhibiting T-cell engagement and reducing the efficacy of checkpoint inhibitors. Polyamidoamine hydroxyl dendrimers (HDs) target TAM without the need of a targeting ligand and are retained by TAMs for up to 1 month allowing radiation to deposit in the tumor.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, primarily due to its dense, desmoplastic and immunosuppressive tumor microenvironment (TME) that hinders the efficacy of immune checkpoint inhibitors such as anti-programmed cell death 1 (PD-1).
Carbonic anhydrase IX (CAIX, CA9) is a membrane-associated isoform of the α-carbonic anhydrase enzyme family, involved in pH regulation and the acidification of the tumor microenvironment (TME) in solid tumors. It is widely recognized as a marker of tumor hypoxia and serves as a prognostic indicator in multiple human cancers.
Esophageal cancer is a malignant disease with high incidence and mortality, where esophageal squamous cell carcinoma (ESCC) is the most common histological subtype. To improve therapeutic approaches for ESCC, it is key to explore the mechanisms behind the disease and find targeted inhibitors.
Degradation is a therapeutic strategy that could offer possibilities to get at currently undruggable target proteins. In targeted degradation, compounds induce interactions between a target protein and a protein that can tag the target for degradation. In principle, there are several pathways that could be used for such tagging; the most attention has gone to ubiquitin ligases, in particular cereblon, a protein that is part of a ubiquitin ligase complex and the target of several approved drugs.
The first systematic whole genome sequencing study of how chemotherapy damages healthy tissues has shown that many, but not all, of these agents cause mutations and premature aging of normal blood cells.
Zhuhai Yufan Biotechnologies Co. Ltd. has identified molecular glue degraders comprising an E3 ubiquitin protein ligase-binding agent covalently bound to a DNA-binding protein Ikaros (IKZF1)-targeting moiety acting as IKZF1 degradation inducers potentially useful for the treatment of cancer, autoimmune disease, neurodegeneration and inflammatory disorders.
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