B-cell lymphoma 6 (BCL6) is an essential transcriptional factor for the humoral immune response. However, genomic deregulation of BCL6 contributes to the development of different types of lymphoma such as diffuse large B-cell lymphoma (DLBCL).
Shanghai Qilu Pharmaceutical Research and Development Centre Ltd. has identified proteolysis targeting chimeras (PROTACs) comprising an E3 ubiquitin ligase cereblon (CRBN)-binding moiety coupled to an interleukin-1 receptor-associated kinase 4 (IRAK-4)-targeting moiety through a linker.
A new series of proteolytic targeting chimeras (PROTACs) was designed by Zhejiang University of Technology scientists based on a previously described PD-L1 inhibitor, and systematic screening of ligands and linkers, combined with structure-activity relationship analysis of the degraders, led to the identification of compounds [I] and [II] as the most active candidates.
The University of Michigan has identified proteolysis targeting chimeric (PROTACs) compounds comprising cereblon (CRBN) ligands covalently bonded to a CREB-binding protein (CREBBP; CBP) and/or histone acetyltransferase KAT3B (p300)-targeting moiety through a linker. They are described as potentially useful for the treatment of cancer, autoimmune and inflammatory disorders.
A paper from Shenzhen University and affiliated organizations covers the discovery of a novel bromodomain-containing protein 4 (BRD4)-specific proteolysis-targeting chimera (PROTAC).
Scientists at Livzon Pharmaceutical Group Inc., Shanghai Institute of Organic Chemistry and the University of Michigan have identified proteolysis targeting chimeras (PROTACs) comprising an E3 ubiquitin ligase binding moiety covalently bound to a cyclin-dependent kinase 12 (CDK12) and 13 (CDK13) targeting moiety through a linker reported to be useful for the treatment of cancer.
The University of Michigan has published details on the discovery and preclinical characterization of a new potent and selective proteolysis targeting chimera (PROTAC) degrader of BRD9, CW-3308. Synthesis and optimization of two different cereblon ligands led to the discovery of a novel series of highly potent BRD9 degraders, with CW-3308 selected as the lead candidate.
Massachusetts Institute of Technology has described proteolysis targeting chimeras (PROTACs) comprising an E3 ubiquitin ligase-binding agent coupled to cyclin-dependent kinase 9 (CDK9)-targeting moiety via linkers acting as CDK9 degradation inducers reported to be useful for the treatment of cancer.
Chia Tai Tianqing Pharmaceutical Group Co. Ltd. has discovered proteolysis targeting chimeras (PROTACs) compounds comprising Von Hippel-Lindau disease tumor suppressor (VHL)-binding moiety covalently linked to Bcl-2-like protein 1 (Bcl-xl; Bcl-X; BCL2L1)-targeting moiety through a linker. They are reported to be useful for the treatment of cancer.
The University of Michigan has identified proteolysis targeting chimeras (PROTACs) comprising cereblon (CRBN) ligands coupled to signal transducer and activator of transcription 3 (STAT3)-targeting moiety via linker acting as STAT3 degradation inducers.
