Characterization and structure-activity relationships of indenoisoquinoline-derived topoisomerase I inhibitors in unsilencing the dormant Ube3a gene associated with Angelman syndrome

ConclusionsWe provide pharmacological profiles of indenoisoquinoline-derived Top1 inhibitors as paternalUbe3a unsilencers. All 13 tested compounds were effective at unsilencing paternalUbe3a, although with variable efficacy and potency. Indotecan (LMP400) demonstrated a better pharmacological profile ofUbe3a unsilencing compared to our previous lead compound, topotecan. Taken together, indotecan and its structural analogues are potential AS therapeutics whose translational potential in AS treatment should be further assessed.
Source: Molecular Autism - Category: Molecular Biology Source Type: research