Background:

NMDI14 is a nonsense mediated RNA decay (NMD) inhibitor.

NMDI14 is a nonsense mediated RNA decay (NMD) inhibitor. Treating cells with NMDI14 for 6 hours leads to an increase of PTC 39 β globin to 12%, a relative four-fold increase that, if resulting in biologically active hemoglobin, would be sufficient to ameliorate the clinical symptoms of thalassemia. Three days of treatment with NMDI14 results in no decrease in cell counts, demonstrating that the pharmacological inhibition of NMD can be achieved without subtle changes in proliferation. 941 genes are increased >1.5 fold with NMDI14. The treatment of N417 cells with NMDI14 for 6 hours leads to a steady state expression of p53 similar to that seen in U2OS cells. NMDI14 significantly increases the stability of PTC mutated p53 mRNA in N417 cells, without altering the stability of wild-type p53 in NMDI treated U2OS cells[1].

[1]. Martin L, et al. Identification and characterization of small molecules that inhibit nonsense-mediated RNA decay and suppress nonsense p53 mutations. Cancer Res. 2014 Jun 1;74(11):3104-1