SK5527

SK5527 (0.01-10000 nM, 1-48 h) induces degradation AURKA MYCN in neuroblastoma and benign cell lines HEK293T, RPE), exhibits the high potency in MYCN-amplified cells (IMR-32, NGP, SJNB-8; SK-N-BE(2)-C with DC₅₀s = 6 ,2 ,10 and 73 nM), shows reduced activity in other lines (SK-N-BE(2)-C, SK-N-AS, SJNB-1) with a hook effect, induces MYCN depletion as a secondary delayed consequence of AURKA degradation and requires concomitant engagement of both AURKA and CRBN to exert the degradation effect in MYCN amplified cells IMR-32, NGP, SJNB-8, SK-N-BE(2)-C with GI₅₀s = 15, 21, 63, 477 nM;in non- amplified cells SK-N-SH, SK-N-AS and SJNB-1 with GI₅₀s = 244, 654, 8635 nM; in benign immortalized cell RPE and HEK293T with GI₅₀s = 460 and 408 nM^[1].
SK5527 (10-10000 nM, 72 h) effectively inhibits neuroblastoma cells (IMR-32, NGP, SJNB 8 , SKN-SH, SK-N-BE(2)-C and SJNB-1) growth^[1].
SK5527 (100-1000 nM, 3 h) requires both AURKA and CRBN binding for the activity, significantly engages AURKA with excellent kinome-wide selectivity, upregulates PLK1 and downregulates HAND2 and ESCO2 but GSPT1, CSNK1A1, ZFP91, SALL4, ZNF654, ZNF787, E4F1, and PATZ1^[1].
SK5527 exhibites only modest inhibitory effects in the benign immortalized cell lines HEK293T and RPE, despite potent AURKA degradation, with GI50 values of approximately 0.5 μM^[1].
SK5527 (10-1000 nM, 24-72 h) is limited by MDR1-Mediated Drug Efflux in SKN-SH, SK-N-BE(2)-C, SJNB-1, NGP, SJNB-8, IMR-32B but SK-N-AS (due to the low CRBN expression)^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.