nTRD22

nTRD22 is an allosteric modulator that targets the RNA binding properties of TDP-43. It binds to the TDP-43 N-terminal domain, leading to an allosteric regulation that reduces the protein's RNA binding capacity. Additionally, nTRD22 decreases the level of TDP-43 protein in primary motor neurons and alleviates motor dysfunction in amyotrophic lateral sclerosis (ALS) models. This compound is applicable for research related to ALS.

nTRD22, when present in concentrations from 0.03 μM to 1 mM, exhibits an apparent Kd of 145 μM for binding to full-length TDP-43 (1 - 260), and an apparent Kd of 96 μM for the N-terminal domain TDP-43 (1 - 102). In alpha experiments, nTRD22 inhibits the binding of TDP-43 (1 - 260) to UG6 RNA with an IC50 of approximately 100 μM. Additionally, nTRD22 in the range of 0.1-500 μM can inhibit the interaction between TDP-43 (1 - 260) and (UG)6 RNA, showing an IC50 of about 145 μM, and in SPR experiments, it achieves an inhibition rate of around 30% for this interaction.

nTRD22 (50 μM; feed medication) significantly alleviates motor dysfunction in an ALS fruit fly model, with a more pronounced rescue effect observed in aged flies.