Figure 2.

Strategies for direct and indirect targeting of MYCN. Different approaches have been developed to hinder MYCN activity, including inhibition of MYCN gene transcription, disruption of the dimerization with its transcriptional partner MAX, induction of MYCN protein destabilization, inhibition of MYCN-promoted cellular processes as well as immunotherapy. Specific inhibitors are highlighted in red. Solid lines indicate direct activity. Dashed lines indicate different protein status (inactive monomeric, active dimeric and degradation-targeted phosphorylated MYCN). PI3K: phosphoinositide 3-kinase; AKT: protein kinase B; GSK3ß: glycogen synthase kinase 3 beta; mTOR, mammalian target of rapamycin; BRD, bromodomain; BET, bromodomain and extra terminal domain; Ub: ubiquitin.