dAURK-4 is a selective AURKA PROTAC degrader. dAURK-4 promotes ubiquitination and degradation of AURKA. dAURK-4 can be used in the research of glioblastoma and multiple myeloma [1] [2]. (Pink: Aurora A ligand; Blue: Cereblon ligand; Black: linker ).
In Vitro, dAURK-4 (1 μM; 5 h) potently and selectively degrades AURKA in MOLT-4 T-lymphoblastic leukemia cells, while exhibits weak activity against AURKB[2]. dAURK-4 (125-1000 nM; 4-24 h) induces dose-dependent degradation of AURKA in MM.1S multiple myeloma cells, and achieves nearly complete degradation at concentrations ≥250 nM[2]. dAURK-4 (0.0001-100 μM; 72 h) exhibits better antiproliferative activity than Alisertib in MM.1S multiple myeloma cells, with stronger potency at low concentrations and more significant inhibitory effects on cell viability at high concentrations[2].
References:
[1]. Leconte G A. Developing a Generalizable Approach to Improve the Blood Brain Barrier Permeability of Proteolysis Targeting Chimeras Through Prodrugs[D]. University of California, San Diego, 2023.
[2]. Donovan KA, et al. Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development. Cell. 2020 Dec 10;183(6):1714-1731.e10.
In Vitro, dAURK-4 (1 μM; 5 h) potently and selectively degrades AURKA in MOLT-4 T-lymphoblastic leukemia cells, while exhibits weak activity against AURKB[2]. dAURK-4 (125-1000 nM; 4-24 h) induces dose-dependent degradation of AURKA in MM.1S multiple myeloma cells, and achieves nearly complete degradation at concentrations ≥250 nM[2]. dAURK-4 (0.0001-100 μM; 72 h) exhibits better antiproliferative activity than Alisertib in MM.1S multiple myeloma cells, with stronger potency at low concentrations and more significant inhibitory effects on cell viability at high concentrations[2].
References:
[1]. Leconte G A. Developing a Generalizable Approach to Improve the Blood Brain Barrier Permeability of Proteolysis Targeting Chimeras Through Prodrugs[D]. University of California, San Diego, 2023.
[2]. Donovan KA, et al. Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development. Cell. 2020 Dec 10;183(6):1714-1731.e10.