CB-096 is an inhibitor of repeat-associated non-ATG (RAN) translation.¹It selectively binds to the hexanucleotide GGGGCC repeat expansion (r(G₄C₂)^exp) hairpin r(G₄C₂)₈(EC₅₀= 19 µM) over the anti-sense hairpin r(G₂C₄)₈and base-paired construct r(GGCC)₁₀. CB-096 (25 µM) inhibits RAN translation and the formation of nuclear stress granules in HEK293T cells expressing r(G₄C₂)₆₆in anin vitromodel ofC9orf72amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) (c9ALS/FTD). It also induces relaxation of rat thoracic aortic rings pre-contracted with norepinephrine (EC₅₀= 1.81 µM) and decreases systolic arterial pressure in conscious spontaneously hypertensive rats when administered at a dose of 100 mg/kg.²

1.Ursu, A., Wang, K.W., Bush, J.A., et al.Structural features of small molecules targeting the RNA repeat expansion that causes genetically defined ALS/FTDACS Chem. Biol.15(12)3112-3123(2020) 2.Navarrete-VÁzquez, G., Hidalgo-Figueroa, S., Torres-Piedra, M., et al.Synthesis, vasorelaxant activity and antihypertensive effect of benzo[d]imidazole derivativesBioorg. Med. Chem.18(11)3985-3991(2010)