RITA

RITA is an inhibitor of p53-HDM-2 interaction, binds to p53dN, with a K_d of 1.5 nM, and also induces DNA-DNA cross-links. IC50 & Target: Kd: 1.5 nM (p53dN)^[1]
DNA Crosslinker^[2] In Vitro: RITA inhibits p53-HDM-2 interaction, binding to p53dN, with a K_d of 1.5 nM. RITA (10 μM) blocks complex formation between p53 and HDM-2 in HCT116 cells and HDFs and in NHF-ERMyc cells irrespective of c-Myc expression. RITA (0.5 μM) reduces the viability of tumor cells in a wild-type p53-dependent manner. Moreover, RITA (0.1 μM) induces p53-dependent apoptosis. RITA induces p53 but does not via DNA damage-signaling pathway^[1]. RITA (NSC 652287) induces DNA-DNA cross-links. RITA induces G2-M cell cycle arrest at 10 nM and causes apoptosis at 100 nM. RITA (100 nM) also elevates p53 and causes dose-dependent effects on p^21WAF1 protein levels^[2]. RITA inhibits the growth of HeLa and CaSki cells, with IC₅₀s of 1 and 10 μM. In addition, RITA (1 μM) stabilizes p53 by inhibiting p53/E6AP interaction^[3]. In Vivo: RITA (0.1, 1 or 10 mg/kg, i.p.) shows potent antitumor activity in SCID mice bearing HCT116 and HCT116 TP53^−/− xenografts^[1]. RITA (10 mg/kg, i.p.) also suppresses the growth of HeLa cells in SCID mice^[3].