RITA(NSC 652287) induced both DNA-protein and DNA-DNA cross-links with no detectable DNA single-strand breaks. RITA, a drug that, like nutlin-3, can disrupt the p53/Mdm2 interaction.

HDM-2 (human double minute-2; MDM-2 in mouse) is a key negative regulator of p53 that binds to and targets p53 for proteasomal degradation. Overexpression of HDM-2 in some tumors leads to inactivation of p53 thereby allowing tumor cells to escape p53-induced apoptosis.RITA (reactivation of p53 and induction of tumor cell apoptosis) is a small molecule inhibitor of p53-HDM-2 interaction that can reactivate the tumor suppressor function of wild-type p53.It binds to p53 with an apparent Kd of 1.5 nM and prevents interaction with HDM-2 resulting in p53 stabilization, accumulation and activation.RITA potently inhibits the growth of a variety of cancer cell lines in the sub-micromolar range, inducing both DNA-protein and DNA-DNA cross links in human renal cancer cells.RITA reduced tumor size by 90% at a dose of 10 mg/kg in SCID mice bearing HCT116 tumors, and caused complete regression of A-498 tumor cell xenografts in nude mice at a dose of 45 mg/kg.