CB-096 is an inhibitor of repeat-associated non-ATG (RAN) translation.1 It 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)8 and 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)66 in an in vitro model of C9orf72 amyotrophic 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)