RITA

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.{13684} RITA is an inhibitor of the protein-protein interaction between p53 and human double minute-2 (HDM-2).{12386} It binds to p53 with an apparent Kd value of 1.5 nM and prevents the interaction between p53 and HDM-2. RITA induces DNA damage and apoptosis in, as well as inhibits the growth of, A498, TK-10, ACHN, and UO-31 renal carcinoma cells (GI50s = 0.017, 0.032, 22.76, and 41.71 µM, respectively).{13682} In vivo, RITA (10 mg/kg) reduces tumor volume in an HCT116 mouse xenograft model.{12386} It also induces complete tumor regression in an A498 mouse xenograft model when administered at a dose of 45 mg/kg.{13682}