Small-molecule drugs approved for clinical practice or under development that act on RNA targets
| Compound | Molecular Targets and Mechanisms of Action | Clinical Application | Current Status | References |
|---|---|---|---|---|
| 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 synthesis | Antibiotics to treat infections | Approved for medical use | Fourmy 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 synthesis | Antibiotics | Approved for medical use | Brodersen 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 synthesis | Antibiotics | Approved for medical use | Vannuffel 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 synthesis | Antibiotics | Approved for medical use | Ippolito 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 suppression | Treatment of patients with DMD with nonsense mutation | Approved 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 levels | Treatment of patients with SMA | Phase 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 protein | Treatment of patients with SMA | Phase I/II trial (NCT02268552) | Palacino et al., 2015; Cheung et al., 2018; Dangouloff and Servais, 2019 |
| Anthraquinones | Binds to HIV TAR element to inhibit viral replication | Treatment of HIV infection | Preclinical development | Ganser et al., 2018 |
| Benzimidazoles (e.g., Isis-11) | Binds to HCV IRES to inhibit viral replication | Treatment of hepatitis C | Preclinical development | Seth et al., 2005; Paulsen et al., 2010; Dibrov et al., 2012 |
| Ribocils | Binds to FMN riboswitch selectively to suppress riboswitch-targeted gene expression and thus inhibit bacterial growth | Antibiotics | Preclinical development | Howe et al., 2015, 2016; Wang et al., 2017; Rizvi et al., 2018 |
| Targaprimir-96 and its bleomycin A5 conjugate | Binds to pri-miR-96 to inhibit Drosha-mediated processing or induce cleavage of pri-miR-96 | Anticancer | Preclinical development | Velagapudi et al., 2016; Li and Disney, 2018 |
| Targapremir-210 and its conjugate | Binds to pre-miR-210 to inhibit Dicer-mediated processing or recruit RNase L for cleavage | Anticancer | Preclinical development | Costales et al., 2017, 2019b |