AT 1 is a VHL-recruiting BRD4 degrader derived from a JQ1-based BET bromodomain ligand and designed as a selective PROTAC for BRD4. The BRD4-recognition portion binds bromodomain acetyl-lysine reader sites, with public sources emphasizing BRD4 selectivity, while the VHL ligand recruits the von Hippel-Lindau E3 ligase complex. In PROTAC design, AT 1 illustrates how a bromodomain inhibitor scaffold can be converted into a degradation-inducing molecule by attaching an E3-recruiting ligand through a linker that supports ternary-complex formation. Its principal function is to induce proximity between BRD4 and VHL, leading to ubiquitination and proteasome-dependent BRD4 depletion. AT 1 is useful for studying BET-family selectivity, BRD4-dependent transcriptional regulation, linker effects, and experimental differences between bromodomain inhibition and targeted removal of BRD4 protein.
Structure of 2098836-45-2
* For research and manufacturing use only. Not for human or clinical use.
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Target: AT 1 selectively targets BRD4 with negligible degradation of BRD2 and BRD3.
Binding site: Its JQ1-derived ligand binds the acetyl-lysine pocket of BRD4 bromodomains.
Mechanism of action: AT 1 is a VHL-based BRD4 PROTAC rationally designed from ternary-complex structural information to enhance BRD4 selectivity relative to earlier BET degraders. The molecule links a (+)-JQ1-derived BET ligand to a von Hippel-Lindau ligand, enabling cooperative formation of a BRD4–AT 1–VHL ternary complex. This complex positions BRD4 for ubiquitination and proteasome-dependent degradation while sparing closely related BET proteins under reported conditions. AT 1 is useful for investigating BRD4-specific transcriptional functions, ternary-complex cooperativity, and structure-guided optimization of selective degraders.
Applications• PROTAC-Mediated Oncogenic Protein Degradation: AT 1 is utilized to selectively degrade oncogenic proteins implicated in cancer progression. By harnessing the ubiquitin-proteasome system, AT 1 facilitates the targeted degradation of these proteins, offering a powerful approach to study cancer biology and elucidate potential therapeutic targets.
• Targeted Degradation in Neurodegenerative Research: AT 1 serves as a valuable tool in neurodegenerative disease research by enabling the degradation of proteins associated with neuronal damage. This application aids in understanding disease mechanisms and exploring new avenues for therapeutic intervention through selective protein elimination.
• PROTAC-Assisted Kinase Inhibition Studies: Employing AT 1 allows researchers to investigate kinase functions by degrading specific kinases of interest. This targeted approach provides insights into kinase signaling pathways and their roles in various cellular processes, enhancing the understanding of potential drug targets.
• Protein Homeostasis and Cellular Pathways: AT 1 is instrumental in studying protein homeostasis by degrading proteins involved in cellular pathways. This application sheds light on the dynamic regulation of protein levels and their impact on cellular function, contributing to the broader understanding of proteostasis.
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
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