RI-2 is a reversible inhibitor of RAD51 (IC50 = 44.2 μM), a protein that is central to the homologous recombination process initiated upon DNA double-strand breaks and is often overexpressed in a wide range of human cancer cell types. At 150 μM, it has been shown to inhibit DNA repair and to sensitize cancer cells to cross-linking chemotherapy in vitro.
RI-2 is a reversible inhibitor of RAD51 (IC50 = 44.2 μM), a protein that is central to the homologous recombination process initiated upon DNA double-strand breaks and is often overexpressed in a wide range of human cancer cell types. At 150 μM, it has been shown to inhibit DNA repair and to sensitize cancer cells to cross-linking chemotherapy in vitro.[Cayman Chemical]
although ri-2 did exhibit reduced activity relative to ri-1, it did retain enough activity to sensitize cells to mmc cell-based assays. ri-2 exhibited no reactivity toward glutathione after incubation for 24 hours. rad51 protein that had been treated with ri-2 prior to washing exhibited no measurable loss of dna binding activity, even though ri-2 is known to inhibit rad51 with an ic50 of 44.17 μm. this indicates that rad51 inhibition by ri-2 is fully reversible [1].
ri-1, the analogue of ri-2, facilitated mapping of the binding pocket within known crystal structures of rad51. however, this reactivity of ri-1 potentially may limit its development in pre-clinical animal models. ri-1 has been found to exhibit a relatively short half-life, due to reactivity in thiol-containing solutions [1].
[1] budke b, kalin jh, pawlowski m, zelivianskaia as, wu m, kozikowski ap, connell pp. an optimized rad51 inhibitor that disrupts homologous recombination without requiring michael acceptor reactivity. j med chem. 2013 jan 10;56(1):254-63.
