Novel, highly potent PROTACs targeting AURORA-A kinase

Targeted AURKA degradation: Towards new therapeutic agents for neuroblastoma

“…Recently, a preprint describes the discovery of PROTAC HLB-0532259, containing a modified version of Ribociclib as AURKA ligand designed to degrade the AURKA/MYCN complex [16]. More recent efforts led to the discovery of novel PROTACs that make use of the highly selective AURKA-inhibitor MK-5108 (Figure 2B) [17]. PROTAC JB301 showed significantly improved degradation potency (DC50,6h 3 nM, Dmax 82%) relative to alisertib-based PROTACs in a leukemic context.…”

PROTAC degraders as chemical probes for studying target biology and target validation

“…118 Recently, a PROTAC, JB301 as well as a matching negative control with improved DC 50 and D max has been published based on the AURORA-A inhibitor MK-5108. 119 JB301 has significantly improved DC 50 (3.1 nM) and D max (82%), but MS based selectivity has only been reported for a closely related analogue with a shorter PEG linker.…”

Targeted Protein Degradation: Clinical Advances in the Field of Oncology

“…The first wave of protein degraders has focused on the oncology fields. The target proteins can be categorized into the following groups: (i) those involved in cancer cell proliferation; (ii) in apoptosis; (iii) in angiogenesis; (iv) in immune evasion or inflammation; and (v) in cancer invasion and metastasis ( Figure 16 ) [ 50 , 51 , 156 , 157 ]. Among those, several have progressed into clinical activities for multiple disease indications ( Table 3 and Table 4 ).…”