AGB1 is a bump-and-hole PROTAC degrader developed for the BromoTag platform, enabling selective degradation of proteins fused to an engineered BRD4 bromodomain variant. Public sources describe it as a fast and selective degrader of BromoTagged proteins, with VHL serving as the recruited ubiquitin-ligase component. The bumped ligand engages the engineered bromodomain tag rather than native BET proteins, while the VHL ligand recruits the VHL-associated ubiquitination machinery. Mechanistically, AGB1 forms a cooperative complex between the engineered BromoTag and VHL, triggering ubiquitination and proteasomal degradation of the tagged target protein. It is valuable for target-agnostic degradation studies, validation of protein function by rapid induced depletion, chemical-genetic tagging workflows, selectivity benchmarking, and experiments requiring degradation of proteins for which no high-affinity endogenous ligand is available.
Structure of 2776190-62-4
* For research and manufacturing use only. Not for human or clinical use.
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Target: AGB1 targets BromoTag-engineered proteins, including Brd4BD2L387A fusion constructs.
Binding site: It binds the engineered BromoTag bromodomain acetyl-lysine pocket created by L387A mutation.
Mechanism of action: AGB1 is a VHL-recruiting bump-and-hole PROTAC developed for the BromoTag inducible degron system. It recognizes an engineered Brd4 bromodomain variant incorporated as a tag on proteins of interest, while its VHL ligand recruits the CUL2VHL E3 ubiquitin ligase complex. This induced proximity enables ubiquitination and rapid proteasomal degradation of tagged proteins with high selectivity over unmodified endogenous proteins. AGB1 supports experimental studies requiring reversible, small-molecule-controlled protein depletion, including time-resolved functional analysis, target validation, and degradation of proteins lacking conventional small-molecule ligands.
Applications• PROTAC-Mediated Kinase Degradation: AGB1 is utilized in research to selectively degrade kinases involved in oncogenic signaling pathways. By inducing proteasomal degradation, researchers can explore the functional consequences of kinase depletion on cancer cell proliferation and survival, offering insights into potential therapeutic targets.
• Targeted Protein Degradation in Neurodegeneration: AGB1 serves as a valuable tool for investigating the degradation of proteins implicated in neurodegenerative diseases. This application allows scientists to study the effects of reducing aberrant protein levels, providing a deeper understanding of disease mechanisms and potential intervention strategies.
• PROTAC-Driven Signal Transduction Studies: Researchers employ AGB1 to degrade specific signaling proteins, enabling the dissection of complex cellular pathways. This targeted degradation approach facilitates the identification of critical nodes within signaling networks and aids in the development of novel therapeutic strategies.
• Selective Degradation of Oncoproteins: AGB1 is instrumental in the targeted degradation of oncoproteins, allowing researchers to evaluate the impact on tumorigenesis. By specifically eliminating these proteins, studies can reveal vulnerabilities in cancer cells and contribute to the design of targeted cancer therapies.
* 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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