Table 7.
Small Molecule Inhibitors of DNA Repair Proteins—HR.
| Inhibitors Targeting | Enzymes | Pathways | Protein Target | Inhibitor | Mechanism of Action | Clinical Trial |
|---|---|---|---|---|---|---|
| DNA processing | RecA-like NTPases | HR | RAD51 | B02 | Inhibits RAD51 by disrupting RAD51 ability to bind ssDNA [280]. | Pre-clinical development. |
| RI-1 | Contains a chloromaleimide group that reacts with cysteine 319 of RAD51 at the monomer–monomer interface near the ATP active site [281]. | Pre-clinical development. | ||||
| RS-1 | Stabilizes the RAD51 nucleoprotein filament and stimulates RAD51 biochemical activities [282]. | Pre-clinical development. | ||||
| IBR120 | Inhibits RAD51 by mimicking the effect of BRC repeat binding to RAD51 [283]. | Pre-clinical development. | ||||
| RAD52 | RAD52 | D-103 | Inhibits RAD52-mediated ssDNA annealing and inhibits D-loop formation [284]. | Pre-clinical development. | ||
| D-G23 | Inhibits RAD52-mediated ssDNA annealing and inhibits D-loop formation [284]. | Pre-clinical development. | ||||
| AICAR | Disrupts the RAD52-ssDNA interaction [285]. | Pre-clinical development. | ||||
| (−)-Epigallocatechin) | Inhibits RAD52 ssDNA binding [286]. | Pre-clinical development. | ||||
| 6-HidroxyDL-dopa | Disrupts RAD52 recruitment and recombination activity [287]. | Pre-clinical development. | ||||
| RAD54 | RAD54/SENP1 | Streptonigrin (STN) | An antitumor antibiotic that binds RAD54 ATPase domain and inactivates it by generating reactive oxygen species [288]. Recently found to bind to and inhibit SUMO-specific protease, SENP1 [289]. | Used to treat multiple cancer types (since the 1960s); however, induces severe and prolonged bone marrow depression. |