Dataset Information

Development of PROTACs for in vivo AURKA degradation in neuroblastoma

ABSTRACT: Aurora Kinase A (AURKA) is a well-established oncogenic factor and potent drug target in neuroblastoma given its crucial role during mitosis, MYCN-stabilization, DNA damage repair and replication fork stability. We previously reported a highly potent, selective and fast-acting AURKA degrader, SK2188, which inhibited tumor cell growth more potently than its parent inhibitor, indicating potential therapeutic benefits of AURKA degradation compared to inhibition. Despite these promising results, SK2188 showed low exposure and rapid clearance in mice following administration, thus hampering further in vivo evaluation and indicating the need for further chemical optimization. In this study, we describe our structure/activity optimization efforts involving linker rigidification and the integration of alternative cereblon- and AURKA-recruiting ligands. These efforts culminated in the rational design of PROTACs SK4454 and SK5527. This LC-MSMS analysis was performed to analyze the short-term (3h) and long-term (24h) effects of SK5527 on the proteome. Our data confirms SK5527 to have a selective AURKA degradation profile.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Neuroblastoma

SUBMITTER: Teresa Mendes Maia

LAB HEAD: Kaat Durinck

PROVIDER: PXD061539 | Pride | 2025-11-20

REPOSITORIES: Pride

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			Action	DRS
	PRC-6321DIA_UPRC_9606X01749_1p_ionopticks1_PM3_PRC-6321_Durinck_1.raw	Raw
	PRC-6321DIA_UPRC_9606X01751_1p_ionopticks1_PM3_PRC-6321_Durinck_13.raw	Raw
	PRC-6321DIA_UPRC_9606X01753_1p_ionopticks1_PM3_PRC-6321_Durinck_17.raw	Raw
	PRC-6321DIA_UPRC_9606X01755_1p_ionopticks1_PM3_PRC-6321_Durinck_21.raw	Raw
	PRC-6321DIA_UPRC_9606X01757_1p_ionopticks1_PM3_PRC-6321_Durinck_5.raw	Raw

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Development of PROTACs for in vivo AURKA degradation in neuroblastoma

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