CCT400028 is a PROTACs -class degrader that targets the Aurora A (AURKA) kinase. CCT400028 induces ubiquitination and proteasomal degradation of target proteins by recruiting the cereblon (CRBN) E3 ubiquitin ligase. The K D values of CCT400028 against the three subtypes of human AURKA are 71 nM, 2100 nM and >10000 nM, respectively, and its IC50 against human CRBN is 6300 nM. CCT400028 is applicable to relevant research on leukemia, neuroblastoma and glioma [1]. (Pink: Aurora A ligand; Blue: Cereblon ligand; Black: linker).
In Vitro, CCT400028 (0.001-10 μM; 0-24 h) shows no hook effect, potently degrades Aurora A in MV4-11 human pediatric leukemia cells, with a DC50 of 29 nM at 6 h and a DCmax of 85%; it also induces potent and sustained (24 h) Aurora A degradation in human pediatric neuroblastoma Kelly cells[1]. The Aurora A degradation activity of CCT400028 (1 μM; 4 h) in human pediatric neuroblastoma Kelly cells can be blocked by proteasome function inhibitors, Cullin ring ligase activity inhibitors, CRBN-binding inhibitors, and Aurora A-binding inhibitors (inhibitors require 2 h of pre-treatment)[1]. CCT400028 (0.01-10 μM; 72 h) inhibits the viability of human pediatric leukemia cells MV4-11, with a GI50 of 310 nM[1].
References:
[1]. O'Hanlon JA, et al. Unhooking the Hook: Optimization of the Aurora A Targeting PROTAC JB170 to CCT400028, an In Vitro Degrader Chemical Probe. J Med Chem. 2026 Jan 22;69(2):1552-1567.
In Vitro, CCT400028 (0.001-10 μM; 0-24 h) shows no hook effect, potently degrades Aurora A in MV4-11 human pediatric leukemia cells, with a DC50 of 29 nM at 6 h and a DCmax of 85%; it also induces potent and sustained (24 h) Aurora A degradation in human pediatric neuroblastoma Kelly cells[1]. The Aurora A degradation activity of CCT400028 (1 μM; 4 h) in human pediatric neuroblastoma Kelly cells can be blocked by proteasome function inhibitors, Cullin ring ligase activity inhibitors, CRBN-binding inhibitors, and Aurora A-binding inhibitors (inhibitors require 2 h of pre-treatment)[1]. CCT400028 (0.01-10 μM; 72 h) inhibits the viability of human pediatric leukemia cells MV4-11, with a GI50 of 310 nM[1].
References:
[1]. O'Hanlon JA, et al. Unhooking the Hook: Optimization of the Aurora A Targeting PROTAC JB170 to CCT400028, an In Vitro Degrader Chemical Probe. J Med Chem. 2026 Jan 22;69(2):1552-1567.