KCB3602 is a specific small-molecule inhibitor of the Lin28-let-7 interaction with IC50 of 4.8 uM in EMSA assays, shows direct binding to Lin28a with SPR KD of 5.9 uM.
KCB3602 shows similar activities in an EMSA using a different member of the let-7 family (PreE-let-7a-1), also exhibits dose-dependent inhibitory activity in FRET assay.
KCB3602 blocks the engagement of pre-let-7 with Lin28, and this blocking resulted in the complete formation of mature let-7 miRNA, does not affect the activity of Dicer.
KCB3602 exclusively binds to Lin28 cold shock domain (CSD), but not zinc knuckle domain (ZKD).
KCB3602 displays selectivity toward Lin28 proteins over heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1).
KCB3602 selectively restores cellular let-7 microRNA levels, decreases the expression of a panel of oncogenes responsible for cancer stem cell maintenance, and shows potential anticancer activities.