Cereblon E3 Ligase – SD-36(PROTAC) – STAT3 protocol
A proteolysis targeting chimera (PROTAC) is a heterobifunctional small molecule composed of two active domains and a linker, capable of removing specific unwanted proteins. Rather than acting as a conventional enzyme inhibitor, a PROTAC works by inducing selective intracellular proteolysis. PROTACs consist of two covalently linked protein-binding molecules: one capable of engaging an E3 ubiquitin ligase, and another one that binds to a target protein meant for degradation. Cereblon forms an E3 ubiquitin ligase complex with damaged DNA binding protein 1 (DDB1), which then can ubiquitinate other proteins. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor. SD-36 is a potent and efficacious STAT3 PROTAC degrader. It is composed of the STAT3 inhibitor SI-109, a linker, and an analog of Cereblon ligand Lenalidomide for E3 ubiquitin ligase.
The two attached documents investigate this interaction via labeling of Cereblon (MOX-P-103) and STAT3 (MOX-P-104), respectively.
protein – small molecule | PROTACs | ternary complex | Hook effect | MOX-P-103 | MOX-P-104