SR-1114

Target: SR-1114 selectively targets ENL, a YEATS-domain chromatin reader protein.

Binding site: Its ENL ligand binds the acetyl-lysine recognition pocket of the YEATS domain.

Mechanism of action: SR-1114 is a CRBN-recruiting ENL PROTAC designed to deplete ENL through ubiquitin-proteasome pathway engagement. The molecule links an ENL YEATS-domain ligand to a cereblon-binding moiety, promoting induced proximity between ENL and CRL4CRBN ubiquitin ligase machinery. This ternary-complex formation drives ENL ubiquitination and proteasomal degradation, enabling downregulation of ENL-dependent transcriptional programs. In targeted protein degradation studies, SR-1114 is useful for interrogating YEATS-domain reader biology, chromatin-associated gene regulation, leukemia differentiation models, degradation kinetics, and functional consequences of ENL protein removal.

• PROTAC-Mediated Oncogene Degradation: SR-1114 is utilized in cancer research to selectively degrade oncogenic proteins, offering a novel strategy to suppress tumor growth by eliminating proteins that are challenging to target with conventional small molecules.

• Targeted Degradation in Neurodegenerative Disease: This PROTAC facilitates the degradation of misfolded or aggregation-prone proteins implicated in neurodegenerative disorders, providing a promising approach to mitigate proteinopathies by reducing toxic protein accumulation.

• Selective Protein Degradation in Signal Transduction: SR-1114 enables the targeted removal of key signaling proteins, allowing researchers to dissect complex cellular pathways and understand the dynamic regulation of signaling networks through controlled protein turnover.

• PROTAC for Epigenetic Modifier Study: By degrading specific epigenetic regulators, SR-1114 aids in elucidating the role of these proteins in gene expression and chromatin remodeling, offering insights into epigenetic mechanisms and potential therapeutic targets.