Ln268 is a potent Lin28 inhibitor, inhibits Lin28:pre-let-7d complex formation in a dose-dependent manner, inhibits Lin28b at both mRNA and protein level, specifically inhibits various Lin28-positive cancer cells.
Ln268 strongly inhibits cell proliferation in both Lin28b-positive DuNE cells and Lin28a-positive IGORV-1 cells, suppresses Lin28b protein expression.
Ln268 inhibits a panel of genes that are direct let-7 targets, CSC, and NE biomarkers, including HMGA2, IGF2BP1, Oct4, Nanog, ID4, FoxC1, ALDH1A2, FoxO3, CHGA, CHGB, SYP, and SCNG.
Ln268 potently inhibits spheroid growth inhibition in DuNE spheroids with IC50 of 10 uM, blocks the CSC phenotype of cancer cells, suppresses formation of 3D colonies, and inhibits cancer cell proliferation.
VOA1066 cells express both Lin28a and Lin28b proteins at relatively high levels and are extremely sensitive to Ln268 with an IC50 of 0.4 uM.
Ln268 exhibits synergistic effect with cisplatin, etoposide and ARS treatment in DuNE cells.