nTRD22 

nTRD22 is an RNA-binding allosteric modulator targeting TDP-43. nTRD22 binds to the N-terminal domain of TDP-43, thereby allosterically regulating the RNA-binding domain of TDP-43 and reducing its RNA-binding ability. nTRD22 decreases the TDP-43 protein level in primary motor neurons. nTRD22 alleviates motor dysfunction in amyotrophic lateral sclerosis models. nTRD22 is applicable to related research on amyotrophic lateral sclerosis^[1].

nTRD22 (0.03 μM-1 mM) binds to full-length TDP-43₁-₂₆₀ with an apparent K_d of 145 ± 3 μM and to the isolated N-terminal domain TDP-43₁-₁₀₂ with an apparent K_d of 96 ± 36 μM^[1].
nTRD22 inhibits TDP-43₁-₂₆₀ binding to UG₆ RNA with an IC₅₀ of ~100 μM in an alpha assay^[1].
nTRD22 (0.1-500 μM) inhibits TDP-43₁-₂₆₀ binding to (UG)₆ RNA with an IC₅₀ of ~145 μM and achieves ~30% inhibition of the interaction in an SPR assay^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

nTRD22 (50 μM; mixed in diet) significantly alleviates motor deficits in an ALS Drosophila model, with a more prominent rescue effect observed in aged Drosophila^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

413.39

C₁₉H₂₂F₃N₃O₄

1065567-62-5

Solid

White to light yellow

O=C(C1=NOC(COC2=CC=CC(C(F)(F)F)=C2)=C1)NCCN3CCCC(C3)O

Room temperature in continental US; may vary elsewhere.

• [1]. Mollasalehi N, et al. An Allosteric Modulator of RNA Binding Targeting the N-Terminal Domain of TDP-43 Yields Neuroprotective Properties. ACS Chem Biol. 2020;15(11):2854-2859.  [Content Brief]