RITA CAS NO.213261-59-7

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.
ic50 value: 54nm in mcf-7 cells [4]
target: mdm-2/p53
in vitro: [2,2':5',2"-terthiopene] 5,5"-diyldimethanol (1f) displayed promising antiproliferative activity compared to rita (ic50=28 nm in mcf-7 cells and 100 nm in colon cancer hct116 cells, vs. 54 and 0.10 nm, respectively, for rita) [4]. nsc 652287 induced both dna-protein and dna-dna cross-links with no detectable dna single-strand breaks. these dna-protein cross-links (dpc) persisted for at least 12 h after drug removal and their frequency was correlated with cytotoxicity in the renal cell lines studied. the most sensitive renal carcinoma cell line, a498, exhibited cell cycle arrest in g(0)-g(1) and g(2)-m at 10 nm nsc 652287, with increased p53 and p21(waf1) protein. at higher concentrations, nsc 652287 still induced p53 elevation but with p21(waf1) reduction and massive apoptosis [1]. rita induced prominent accumulation and reactivation of p53 in a wild-type tp53-bearing hnc cell line. rita showed maximal growth suppression in tumor cells showing mdm2-dependent p53 degradation. rita promoted apoptosis in association with upregulation of p21, bax, and cleaved caspase-3; notably, the apoptotic response was blocked by pifithrin-α, demonstrating its p53 dependence. with increasing concentrations, rita strongly induced apoptosis rather than g2-phase arrest [2]. by western blot analysis we further confirmed that rita induced activation of p53 in conjunction with up-regulation of phosphorylated ask-1, mkk-4 and c-jun [3].
in vivo: