Our first discovery used an in silico approach targeting the RRMs,47 more specifically the nucleic acid binding interface of RRM1, since mutations inhibiting nucleic acid binding completely reversed ALS phenotypes in TDP-43 overexpressed Drosophila models.48 We validated one compound, rTRD01, through NMR spectroscopy and Microscale Thermophoresis (MST), obtaining a binding constant in the micromolar range (kD = 89.4 ± 0.8 μM), a relatively weak affinity that will be improved using structure activity relationship (SAR) studies. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.