Fig. 5: MYC-RIBOTAC selectively targets MYC in an RNase-L-dependent manner.
From: Programming inactive RNA-binding small molecules into bioactive degraders
a, Schematic of the targeted degradation of the MYC IRES. b, Compound structures. c, The effect of MYC-binder and MYC-RIBOTAC on MYC mRNA levels in HeLa cells, as determined using RT–qPCR. n = 3 biological replicates. d, The effect of MYC-RIBOTAC on MYC protein levels in HeLa cells (n = 3 biological replicates). e, The effect of MYC-RIBOTAC on the proliferation (left) and apoptosis (right) of HeLa cells (n = 3 biological replicates). f, The effect of MYC-RIBOTAC on MYC IRES luciferase reporter in HEK293T cells (left) or on a control reporter lacking the IRES (right)(n = 3 biological replicates). g, Transcriptome-wide changes in HeLa cells treated with MYC-RIBOTAC (10 μM) after treatment for 48 h (n = 3 biological replicates). EGR1 is a well-known downstream target of MYC50. h, Cumulative distribution analysis of the effect of MYC-RIBOTAC and a MYC-selective siRNA on 87 well-validated downstream targets of MYC, or on the downstream targets of HIF-1α, as indicated by a Kolmogorov–Smirnov analysis of their levels relative to all proteins (n = 3 biological replicates). i, The effect of MYC-Ctr and MYC-RIBOTAC on MYC mRNA levels in Namalwa Burkitt lymphoma cells (n = 3 biological replicates) compared with the vehicle (n = 6 biological replicates). j, The effect of MYC-RIBOTAC on MYC protein levels in Namalwa cells (n = 2 biological replicates). k, The effect of MYC-RIBOTAC on the cell cycle of Namalwa cells. n = 2 biological replicates. l, The ability of MYC-RIBOTAC or MYC-Ctr to induce apoptosis of Namalwa cells (n = 2 biological replicates). m, The effect of MYC-RIBOTAC on colony formation of Namalwa cells (n = 2 biological replicates). Data are mean ± s.d. (c–f and i). Statistical significance was determined using a one-way ANOVA adjusted for multiple comparisons (c), two-tailed Student’s t-tests (d–i), Wald’s test (g), or Kolmogorov–Smirnov test (h).
