Table 2.
Pharmacological agents that induce or stabilize R-loops
| Drugs/inhibitors/agents | Target/mechanism of action/remarks | References |
|---|---|---|
| Camptothecin (CPT) and analogues | Traps TOP1 cleavage complexes (TOP1ccs) | (101,139,140,147) |
| JQ1 | Bromodomain and extraterminal domain (BET) protein family inhibitor | (135,194,195) |
| Pladienolide B (Plad-B) | Inhibits the splicing factor SF3B1and in turn inhibits splicing |
(96–98,100,110,162,163) |
| Crosslinking agents like Reactive natural aldehydes and mitomycin c | Degrade BRCA2 causing accumulation of R-loops Can increase R-loop levels, especially in cells without a functioning FA pathway by physical stalling of the transcription machinery which promote R-loop formation |
(181,182,196,197) |
| Pyridostatin/ PDS, Braco-19, and FG | Bind and stabilize G4 quadruplex structures in the displaced strand of R loops which in turn stabilizes DNA: RNA hybrids and helps extension of cotranscriptional R loops Can target BRCA1/2 deficient cancers |
(198) |
| CX-5461 | Inhibits RNA polymerase I transcription and G4 quadruplex ligand Selectively kills tumors with BRCA1/2 deficiency |
(199,200) |
| Romidepsin | HDAC Inhibitor | (201) |
| VX970 and other ATR inhibitors | ATR inhibition and increase replication stress | (30,192,202) |
| SMG1 inhibitor | Inhibits serine/threonine-protein kinase SMG1 and non-sense mediated decay | (99) |
| Anticancer sulphonamides | Target U2AF-related splicing factor coactivator of activating protein-1 for proteasomal degradation | (98,203) |