JB170 is a potent and highly specific PROTAC -mediated AURORA-A ( Aurora Kinase ) degrader ( DC 50 =28 nM) by linking Alisertib, to the Cereblon -binding molecule Thalidomide. JB170 preferentially binds AURORA-A ( EC 50 =193 nM) over AURORA-B (EC 50 =1.4 µM). JB170-mediated S-phase arrest is caused specifically by AURORA-A depletion. JB170 has excellent ability to inhibit non-catalytic function of AURORA-A kinase
In Vitro
JB170 (1 μM; 24-72 hours; MV4-11 cells) mediates Aurora-A depletion inhibiting cancer cell survival. ?\nJB170 (0.01-10 μM; 6 hours; MV4-11 cells) reduces AURORA-A levels. ?\nJB170 (0.5 μM; 12 hours; MV4-11 cells) delays/arrests S-phase progression. ?\nJB170 (0.5 μM; 0-72 hours; MV4-11 cells) induces apoptosis is exclusively caused by targeting AURORA-A. ?\nJB170 (0.1 μM; 0-9 hours; IMR5 cells) shows rapid AURORA-A depletion. JB170 (0~1 μM; 6 hours; MV4-11 cells) strongly attenuates in mutants with respect to AURORA-A. JB170 (0.1 μM; 18 hours; MV4-11 cells) does not activate AURORA-A. JB170 (0~1 μM; 24 hours; IMR5 cells) largely abrogates AURORA-A T217D depletion. JB170 (1 μM; 4 days; IMR5 cells) mediates Aurora-A depletion inhibiting cancer cell survival. JB170 (IMR5 cells) reduces AURORA-A levels by lowering AURORA-A mRNA levels. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: MV4-11 cells Concentration: 1 µM Incubation Time: 24-72 hours Result: After 72 hours, the number of viable cells was 32% of control levels. Western Blot AnalysisCell Line: MV4-11 cells Concentration: 0.01~10 μM Incubation Time: 6 hours Result: Substantial degradation was observed at 100 nM and 1 µM. Apoptosis AnalysisCell Line: MV4-11 cells Concentration: 0.5 µM Incubation Time: 0~72 hours Result: Apoptosis was exclusively caused by targeting AURORA-A. Cell Cycle AnalysisCell Line: MV4-11 cells Concentration: 0.5 µM Incubation Time: 12 hours Result: Delayed or arrested S-phase progression.
Form:Solid
IC50& Target:Aurora A 28 nM (DC 50 ) Aurora A 99 nM (Kd) Aurora A 193 nM (EC 50 ) Cereblon
