Association details:
Evidence Level:
Sensitive: D – Preclinical

1558 / 6 - Targeting CDK9 via the small-molecule inhibitor enitociclib as a therapeutic strategy to treat MYCN-amplified rhabdomyosarcoma and neuroblastoma in children

Published date:
In this study, we investigated the activity of the selective small-molecule CDK9 inhibitor enitociclib (VIP152/BAY1521152) in preclinical models of pediatric MYCN-amplified aRMS and NBL….Significant cytotoxic activity, with IC50 values ranging from 48-182 nM and 39-123 nM was seen for aRMS cells and NBL cells, respectively. SynergyFinder found synergistic effects of enitociclib with irinotecan, carfilzomib, etoposide, bortezomib, selinexor or topotecan tested at clinically relevant concentrations in the aRMS cell line Rh41. Enitociclib induced apoptosis with cleavage of caspase-3 and PARP....Our results suggest that CDK9 inhibition is potentially clinically relevant for MYCN-amplified solid tumors such as aRMS and NBL due to its significant antitumor activity and pharmacologic targetability.