SK4454 is a selective AURKAPROTAC degrader that targets the AURKA protein with an IC50 of 8 nM. It binds to NanoLuc-AURKA with an IC50 of 20 nM. SK4454 effectively reduces MYCN levels in MYCN-amplified neuroblastoma cells, although its activity is limited by MDR1-mediated efflux. In vivo, SK4454 efficiently decreases AURKA levels. It is useful for research related to neuroblastoma.

Aurora A:20 nM

SK4454 (0.01-10000 nM, 1-48 hours) promotes the degradation of AURKA and MYCN in neuroblastoma and benign cell lines (HEK293T, RPE), demonstrating high potency in MYCN-amplified cells (IMR-32, NGP, SJNB-8, SK-N-BE(2)-C with DC 50 values of 6, 8, 23, and 270 nM, respectively) and reduced activity with a hook effect in other lines (SK-N-BE(2)-C, SK-N-AS, SJNB-1). The MYCN depletion induced is a secondary delayed event following AURKA degradation, requiring simultaneous binding to AURKA and CRBN for degradation (GI 50 values of 8, 14, 53, 1111 nM in IMR-32, NGP, SJNB-8, SK-N-BE(2)-C). In non-amplified cells (GI 50 in SK-N-SH, SK-N-AS, and SJNB-1 is 430, 994, 13437 nM, respectively) and benign immortalized cells RPE (GI 50 is 221 nM), similar results are observed. Additionally, SK4454 (10-10000 nM, 72 hours) effectively inhibits the growth of neuroblastoma cells (IMR-32, NGP, SJNB-8, SK-N-SH, SK-N-BE(2)-C, SJNB-1). The activity of SK4454 (10-1000 nM, 24-72 hours) in SK-N-SH, SK-N-BE(2)-C, SJNB-1, NGP, SJNB-8, and IMR-32 cells is limited by MDR1-mediated drug efflux, while SK-N-AS cells show no such limitation due to low CRBN expression.

SK4454 (15 mg/kg, administered either intravenously or intraperitoneally as a single dose) can induce depletion of AURKA protein in xenograft (CDX) mouse models derived from the IMR-32 neuroblastoma cell line.