Home Apoptosis p53 activator - E3 Ligase inhibitor RITA (NSC 652287)

RITA (NSC 652287)

Catalog No.S2781

For research use only.

RITA (NSC 652287) induces both DNA-protein and DNA-DNA cross-links with no detectable DNA single-strand breaks, and also inhibits MDM2-p53 interaction by targeting p53.

RITA (NSC 652287) Chemical Structure

CAS No. 213261-59-7

Selleck's RITA (NSC 652287) has been cited by 8 Publications

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Biological Activity

Description RITA (NSC 652287) induces both DNA-protein and DNA-DNA cross-links with no detectable DNA single-strand breaks, and also inhibits MDM2-p53 interaction by targeting p53.
Features Inducer of DNA cross-links, not a DNA intercalator.
Targets
Mdm2 [1] p53 [3]
()
In vitro

RITA shows a highly selective pattern of differential cytotoxic activity in the tumor cell lines, due to cellular accumulation to the cytosolic (S100) fraction. RITA also inhibits the growth of other renal cell lines including ACHN and UO-31 with IC50 of 13 μM and 37 μM, respectively. [1] RITA (10 nM) causes cell cycle arrest with accumulation of cells at the G2-M phase and induces DNA fragmentation and apoptosis at 100 nM, both with evaluated p53 protein levels. RITA (30 nM) also induces both DNA-protein and DNA-DNA cross-links in A498 cells. Meanwhile RITA has no effects on top1-mediated relaxation of supercoiled SV40 DNA. [2] RITA significantly suppresses the growth of HCT116 cells (97%) but only slightly inhibits the growth of HCT116 TP53-/- cells (13%). RITA is much more efficient at growth suppression in wild-type p53-expressing tumor cell lines than in cell lines lacking p53 and those expressing mutant p53. RITA binds full-length p53 but not glutathione S-transferase (GST) protein or HDM-2 (a key regulator of p53 is strongly supported by the rescue of embryonic lethality of MDM2). RITA blocks p53−HDM-2 interaction and p53 ubiquitination. RITA substantially decreases the amount of HDM-2 that is co-precipitated with p53, although both proteins are upregulated. RITA prevents interactions between the purified GST-p53 and 6XHis-tagged His-HDM-2 proteins. [3] RITA is shown to induce apoptosis by promoting p53Ser46 phosphorylation. [4] RITA induces activation of p53 in conjunction with up-regulation of phosphorylated ASK-1, MKK-4 and c-Jun. RITA induces the activation of JNK signaling. [5] But On the contrary, another results by nuclear magnetic resonance (NMR) show that RITA does not block the formation of the complex between p53 (residues 1-312) and the N-terminal p53-binding domain of MDM2 (residues 1-118), which is highly probable that the binding of RITA requires native conformation of p53. [6]
In vivo RITA is well tolerated in mice after intraperitoneal administration, with no observable weight loss at doses up to 10 mg/kg during 1 month. After five injections of 0.1 mg/kg of RITA, the growth of the HCT116 tumors is suppressed by 40%, without apparent effects on the HCT116 TP53-/- tumors. At a dose of 1 or 10 mg/kg, RITA shows strong antitumor activity. Five 1 mg/kg injections of RITA results in a more than twofold decrease in the growth rate of p53-positive xenografts without any effect on p53-null xenografts. HCT116 tumors are 90% smaller in mice treated with 10 mg/kg of RITA than in control untreated mice. RITA inhibits the tumor growth in a wild-type p53−dependent manner. [3]

Protocol (from reference)

Cell Research:[1]
  • Cell lines: HCT116 cells and HCT116 TP53-/- cells
  • Concentrations: 0.1 nM - 1 mM, 10 mM stocked in DMSO
  • Incubation Time: 48 hours
  • Method: 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
Animal Research:[3]
  • Animal Models: SCID mice carrying HCT116 and HCT116 TP53-/- xenografts
  • Dosages: 0.1 mg/kg, 1 mg/kg or 10 mg/kg
  • Administration: Administered via i.v. or i.p.

Solubility (25°C)

In vitro

 DMSO 58 mg/mL
(198.37 mM)
Ethanol 8 mg/mL
(27.36 mM)
Water Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
30% propylene glycol, 5% Tween 80, 65% D5W
For best results, use promptly after mixing.

 30 mg/mL

Chemical Information

Molecular Weight 292.37
Formula

C14H12O3S2
CAS No. 213261-59-7
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1=C(SC(=C1)C2=CC=C(O2)C3=CC=C(S3)CO)CO

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Molarity Calculator

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT05153551 Not yet recruiting Other: Play-based assessment (RITA-T) Autism Spectrum Disorder University of Michigan|Blue Cross Blue Shield of Michigan Foundation January 2022 Not Applicable
NCT03806127 Completed Drug: Vibegron|Drug: Placebo Irritable Bowel Syndrome Urovant Sciences GmbH December 31 2018 Phase 2
NCT00779025 Completed Device: PD-F-5254|Device: 10855-096 Coitus Johnson & Johnson Consumer and Personal Products Worldwide January 2008 Not Applicable

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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