Targapremir-200c (TGP-200c) is a structure-specific, small molecule inhibitor of miR-200c precursor (pre-miR-200c), binds to the Dicer site of pre-miR-200c with Kd of 50 nM.TGP-200c inhibits Dicer processing of pre-miR-200c with IC50 320 nM, selectively engages pre-miR-200c in cells.TGP-200c potently inhibits miR-200c biogenesis selectively across the miRnome and modulates the downstream miR-200c pathway.TGP-200c selectively inhibits miR-200c over other miR-200 family members by recognizing the 1x1 UU internal loop unique to pre-miR-200c and an adjacent AU base pair simultaneously.TGP-200c selectively rescues a miR-200c-mediated phenotype in MIN6 cells, induces anti-apoptotic phenotype, modulates various T2D-related pathways, including insulin signaling and metabolism, represses pro-cell death factors and promotes β cell survival in specific ways.
