Small-molecule drugs approved for clinical practice or under development that act on RNA targets

CompoundMolecular Targets and Mechanisms of ActionClinical ApplicationCurrent StatusReferences
Aminoglycosides (e.g., streptomycin, neomycin, paromomycin, etc.)Binds to 16S rRNA in the decoding region A-site on the 30S subunit to induce misreading of the genetic code and thus inhibit protein synthesisAntibiotics to treat infectionsApproved for medical useFourmy et al., 1996; Ogle et al., 2001; Demeshkina et al., 2012; Demirci et al., 2013
Tetracyclines (e.g., tetracycline, tigecycline, etc.)Binds to 16S rRNA in the A-site on the 30S subunit to block tRNA binding and thus inhibit protein synthesisAntibioticsApproved for medical useBrodersen et al., 2000; Anokhina et al., 2004; Schedlbauer et al., 2015
Macrolides (e.g., erythromycin, telithromycin, etc.)Binds to 23S rRNA in the NPET of the 50S subunit to block egress of nascent polypeptide and thus inhibit protein synthesisAntibioticsApproved for medical useVannuffel and Cocito, 1996; Hansen et al., 2002; Berisio et al., 2003; Tu et al., 2005; Bulkley et al., 2010
Oxazolidinones (e.g., linezolid, tedizolid, etc.)Binds to 23S rRNA in the A-site cleft near PTC of 50S subunit to interfere with tRNA accommodation and thus inhibit protein synthesisAntibioticsApproved for medical useIppolito et al., 2008; Wilson et al., 2008; Deak et al., 2016
Translarna (ataluren; PTC124)Targets ribosome to promote insertion of near-cognate tRNAs at the site of the dystrophin gene toward nonsense suppressionTreatment of patients with DMD with nonsense mutationApproved in Europe; phase III trial in the United States (NCT03179631)Bushby et al., 2014; Ryan, 2014; Haas et al., 2015; Roy et al., 2016; McDonald et al., 2017
Risdiplam (RG7916; RO7034067)Interacts with SMN2 pre-mRNA and modifies RNA splicing to increase SMN protein expression levelsTreatment of patients with SMAPhase II/III trial (NCT02913482)Ratni et al., 2016, 2018; Poirier et al., 2018; Sturm et al., 2019
Branaplam (LMI070; NVS-SM1)Stabilizes the spliceosome and SMN2 pre-mRNA interactions to enhance SMN2 pre-mRNA splicing and thus increase expression of full-length SMN mRNA and functional proteinTreatment of patients with SMAPhase I/II trial (NCT02268552)Palacino et al., 2015; Cheung et al., 2018; Dangouloff and Servais, 2019
AnthraquinonesBinds to HIV TAR element to inhibit viral replicationTreatment of HIV infectionPreclinical developmentGanser et al., 2018
Benzimidazoles (e.g., Isis-11)Binds to HCV IRES to inhibit viral replicationTreatment of hepatitis CPreclinical developmentSeth et al., 2005; Paulsen et al., 2010; Dibrov et al., 2012
RibocilsBinds to FMN riboswitch selectively to suppress riboswitch-targeted gene expression and thus inhibit bacterial growthAntibioticsPreclinical developmentHowe et al., 2015, 2016; Wang et al., 2017; Rizvi et al., 2018
Targaprimir-96 and its bleomycin A5 conjugateBinds to pri-miR-96 to inhibit Drosha-mediated processing or induce cleavage of pri-miR-96AnticancerPreclinical developmentVelagapudi et al., 2016; Li and Disney, 2018
Targapremir-210 and its conjugateBinds to pre-miR-210 to inhibit Dicer-mediated processing or recruit RNase L for cleavageAnticancerPreclinical developmentCostales et al., 2017, 2019b