NMDI14

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

Signaling Pathways >> Others >> Others

Research Areas >> Cancer

NMD[1]

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].

To assess viability cells are cultured in 6 well dishes and incubated with DMSO, G418, NMDI alone or G418 with NMDI together for the indicated hours. After incubations, cells and media are collected and cells viability is measured. To assess cell proliferation U2OS, Hela and BJ-htert cells are cultured in 6 well plates and, after 24 hrs, treated with NMDI14 for 0, 24, 48 and 72hrs. The cells are collected and viable cells are counted by using the Countess Automated Cell Counter[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

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