RITA

SKU: orb1307419

Description

RITA (NSC-652287) is a small molecule that disrupts the p53-MDM2 interaction, similar to nutlin-3. It induces DNA-DNA and DNA-protein crosslinks without causing detectable single-strand breaks. This compound is used in cancer research to study p53 reactivation and its effects in both cellular and animal models.

Research Area

Cell Biology

Key Properties

• CAS Number: 213261-59-7
• MW: 292.4
• Purity: 97.76% (May vary between batches)
• Formula: C₁₄H₁₂O₃S₂
• SMILES: OCc1ccc(s1)-c1ccc(o1)-c1ccc(CO)s1
• Target: Transcription factor
• Solubility: Soluble in DMSO (up to 20 mg/ml)

Bioactivity

• Target IC50:
  p53dN:1.5 nM (Kd)
• In Vivo:
  RITA (10 nM) caused cell cycle arrest and accumulation of cells in the G2-M phase, and at 100 nM it induced DNA fragmentation and apoptosis and increased p53 protein levels. RITA (30 nM) also induced the production of DNA-protein and DNA-DNA crosslinks in A498 cells. At the same time, RITA did not affect top1-regulated superhelical SV40 DNA loosening. RITA significantly inhibited HCT116 cell growth (97%) and slightly inhibited HCT116 TP53-/- cell growth (13%). RITA inhibited the growth of wild-type p53-expressing cells more effectively than that of cells lacking p53 or with p53 mutation. When acting on tumor cells, RITA showed a high degree of selectivity for different toxicities due to the accumulation of cytoplasmic (S100) fractions.RITA bound to full-length p53 but not to glutathione S-transferase proteins or HDM-2.RITA also inhibited the growth of other renal cell lines including ACHN and UO-31 (IC50: 13 μM and 37 μM). RITA blocked p53-HDM-2 interaction and p53 ubiquitination.RITA caused a significant decrease in the amount of HDM-2 co-precipitated with p53, although both proteins were up-regulated.RITA blocked the interaction between 6XHis-tagged His-HDM-2 protein and purified GST-p53. By promoting p53Ser46 phosphorylation, RITA induces apoptosis. RITA induced p53 activation and showed upregulation of phosphorylated MKK-4, ASK-1 and c-Jun. It also induced JNK signaling activation. NMR results showed that RITA did not block the formation of the complex between the N-terminal p53-binding domain (residues 1-118) and p53 (residues 1-312) of MDM2, which may be related to the fact that the binding of RITA requires the natural conformation of p53.
• In Vitro:
  RITA (10 nM) caused cell cycle arrest and accumulation of cells in the G2-M phase, and at 100 nM it induced DNA fragmentation and apoptosis and increased p53 protein levels. RITA (30 nM) also induced the production of DNA-protein and DNA-DNA crosslinks in A498 cells. At the same time, RITA did not affect top1-regulated superhelical SV40 DNA loosening. RITA significantly inhibited HCT116 cell growth (97%) and slightly inhibited HCT116 TP53-/- cell growth (13%). RITA inhibited the growth of wild-type p53-expressing cells more effectively than that of cells lacking p53 or with p53 mutation. When acting on tumor cells, RITA showed a high degree of selectivity for different toxicities due to the accumulation of cytoplasmic (S100) fractions.RITA bound to full-length p53 but not to glutathione S-transferase proteins or HDM-2.RITA also inhibited the growth of other renal cell lines including ACHN and UO-31 (IC50: 13 μM and 37 μM). RITA blocked p53-HDM-2 interaction and p53 ubiquitination.RITA caused a significant decrease in the amount of HDM-2 co-precipitated with p53, although both proteins were up-regulated.RITA blocked the interaction between 6XHis-tagged His-HDM-2 protein and purified GST-p53. By promoting p53Ser46 phosphorylation, RITA induces apoptosis. RITA induced p53 activation and showed upregulation of phosphorylated MKK-4, ASK-1 and c-Jun. It also induced JNK signaling activation. NMR results showed that RITA did not block the formation of the complex between the N-terminal p53-binding domain (residues 1-118) and p53 (residues 1-312) of MDM2, which may be related to the fact that the binding of RITA requires the natural conformation of p53.
• Cell Research:
  Examination to assess susceptibility of cells to RITA (0.1 nM - 1 mM) is done using the XTT assay. Cells are inoculated into 96-well flat-bottom plates at a density of 1500 cells per well and incubated for 24 hours at 37 °C in a humidified 5% CO2 5% air atmosphere. Serial concentrations of RITA in DMSO are added to the wells, and sensitivity is determined 48 hours after the addition of RIT(Only for Reference)

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

NSC 652287

Compound Identifiers

PubChem CID

374536