JB300 is a PROTAC degrader that selectively targets and degrades AURORA-A by recruiting cereblon, with EC 50 values of 373 nM and 193 nM in intact cells and permeabilized cells, respectively. JB300 can be used in studies related to acute myeloid leukemia and targeted protein degradation mechanisms [1]. (Pink: Aurora A ligand; Blue: Cereblon ligand; Black: linker ).
In Vitro, JB300 binds to AURORA-A in intact HEK293T cells with an EC50 of 373.0 nM[1]. JB300 binds to AURORA-A in digitonin-permeabilized HEK293T cells with an EC50 of 193.0 nM, exhibiting excellent cell permeability[1]. JB300 degrades AURORA-A in MV4-11AURORA-HiBiT cells, with a DC50 of 30 nM, and the maximum degradation rate reaches 78% after 6 hours of incubation[1]. Incubation of MV4-11 cells with JB300 (0.002-10 μM; 6 h) selectively degrades endogenous AURORA-A but not AURORA-B in a dose-dependent manner, with a hook effect observed at 10 μM[1]. JB300 (0.625 μM; 6 h)-induced AURORA-A degradation in MV4-11 cells is completely blocked by MG132 (10 μM); co-incubation with MK-5108 (1 μM) or Thalidomide (1, 10, 20 μM) also completely blocks AURORA-A depletion, indicating that this process depends on AURORA-A, Cereblon binding and the proteasome[1]. In quantitative proteomic analysis of MV4-11 cells, JB300 (0.625 μM; 6 h) induces the most significant reduction in AURORA-A among 5469 detected proteins (log2FC = -2.3); PTK2B shows only a weak but significant decrease (log2FC = -0.7), while no significant changes occur in other proteins or known Cereblon neosubstrates[1]. JB300 (0.625 μM; 18 h) reduces BrdU signals in the S phase of MV4-11 cells and induces mild G2/M cell cycle arrest[1]. JB300 (0.625 μM; 1-72 h) induces rapid and persistent degradation of AURORA-A in MV4-11AURORA-HiBiT cells; after a single dose of 0.625 μM, the degradation reaches the maximum level at 9 h and persists up to 72 h[1]. JB300 (incubated for 72 h) reduces the viability of MV4-11 cells, with an EC50 of 478 nM after 72 h of incubation[1].
References:
[1]. Bozilovic J, et al. Novel, highly potent PROTACs targeting AURORA-A kinase. Curr Res Chem Biol. 2022;2:100032.
In Vitro, JB300 binds to AURORA-A in intact HEK293T cells with an EC50 of 373.0 nM[1]. JB300 binds to AURORA-A in digitonin-permeabilized HEK293T cells with an EC50 of 193.0 nM, exhibiting excellent cell permeability[1]. JB300 degrades AURORA-A in MV4-11AURORA-HiBiT cells, with a DC50 of 30 nM, and the maximum degradation rate reaches 78% after 6 hours of incubation[1]. Incubation of MV4-11 cells with JB300 (0.002-10 μM; 6 h) selectively degrades endogenous AURORA-A but not AURORA-B in a dose-dependent manner, with a hook effect observed at 10 μM[1]. JB300 (0.625 μM; 6 h)-induced AURORA-A degradation in MV4-11 cells is completely blocked by MG132 (10 μM); co-incubation with MK-5108 (1 μM) or Thalidomide (1, 10, 20 μM) also completely blocks AURORA-A depletion, indicating that this process depends on AURORA-A, Cereblon binding and the proteasome[1]. In quantitative proteomic analysis of MV4-11 cells, JB300 (0.625 μM; 6 h) induces the most significant reduction in AURORA-A among 5469 detected proteins (log2FC = -2.3); PTK2B shows only a weak but significant decrease (log2FC = -0.7), while no significant changes occur in other proteins or known Cereblon neosubstrates[1]. JB300 (0.625 μM; 18 h) reduces BrdU signals in the S phase of MV4-11 cells and induces mild G2/M cell cycle arrest[1]. JB300 (0.625 μM; 1-72 h) induces rapid and persistent degradation of AURORA-A in MV4-11AURORA-HiBiT cells; after a single dose of 0.625 μM, the degradation reaches the maximum level at 9 h and persists up to 72 h[1]. JB300 (incubated for 72 h) reduces the viability of MV4-11 cells, with an EC50 of 478 nM after 72 h of incubation[1].
References:
[1]. Bozilovic J, et al. Novel, highly potent PROTACs targeting AURORA-A kinase. Curr Res Chem Biol. 2022;2:100032.