β-NF-JQ1

β-NF-JQ1 is a BRD2/3/4 PROTAC degrader. β-NF-JQ1 recruits the AhR E3 ligase complex to BRD2, BRD3 and BRD4, induces AhR- BRD interaction, and mediates AhR-dependent degradation through the proximity effect between the target protein and AhR. β-NF-JQ1 acts as an antiproliferative and cytotoxic agent that induces anticancer activity associated with BRD protein knockdown. β-NF-JQ1 can be used for research on breast cancer and neuroblastoma ^{[1] [2]}. (Pink: BRD4 and BRD2 and BRD3 ligand; Blue: Aryl Hydrocarbon Receptor ligand; Black: linker ).

In Vitro, β-NF-JQ1 (0.01-30 μM; 24 h) induces concentration-dependent degradation of BRD3, BRD4 and BRD2 proteins in MCF-7 cells, with the strongest effect on BRD3 at the highest concentration of 30 μM^[1]. β-NF-JQ1 (30 μM; 6 h, co-treated with 10 μM MG132 ) induces the interaction between AhR and BRD2, BRD4 proteins in MCF-7 cells^[1]. β-NF-JQ1 selectively degrades BRD3, but not BRD2 or BRD4, in AhR-negative human neuroblastoma SH-SY5Y cells via an AhR-independent mechanism^[2]. β-NF-JQ1 (0.01-30 μM; 72 h) potently inhibits the growth of MCF-7 cells and induces concentration-dependent cytotoxicity^[1]. β-NF-JQ1 (0-30 μM; 48 h, following 24 h siRNA transfection) induces growth inhibition in MCF-7 cells, and this effect is dependent on AhR^[1]. β-NF-JQ1 (3-30 μM; 48 h) induces apoptosis in MCF-7 cells, which is confirmed by the cleavage of caspase-7, PARP and lamin B1, accompanied by the degradation of BRD4, BRD2, BRD3 and c-Myc proteins^[1].

References:
[1]. Ohoka N, et al. Development of Small Molecule Chimeras That Recruit AhR E3 Ligase to Target Proteins. ACS chemical biology. 2019 Dec 20;14(12):2822-2832.
[2]. Shoda T, et al. Targeted Protein Degradation by Chimeric Compounds using Hydrophobic E3 Ligands and Adamantane Moiety. Pharmaceuticals (Basel, Switzerland). 2020 Feb 25;13(3):34.