NMDI14 is an inhibitor of nonsense mediated RNA decay (NMD).

NMDI14 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[1].NMDI14, an inhibitor of nonsense-mediated mRNA decay (NMD), restored W1282X mRNA to almost 50% of WT levels in the parental NE cells. RNA-seq of the NE cells homozygous for W1282X showed that CFTR transcript level was reduced to 1.7% of WT (p-value: 4.6e-3). Negligible truncated CFTR protein was generated by Flp-In 293 cells stably expressing the W1282X EMG even though CFTR transcript was well above levels observed in the parents and proband. Finally,NMD inhibition improved the stability and response to correctors of W1282X-CFTR protein expressed in the Flp-In-293 cells[2].