RITA

製品コードS2781 バッチS278101

印刷

化学情報

Chemical Structure Synonyms NSC 652287 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C14H12O3S2
分子量 292.37 CAS No. 213261-59-7
Solubility (25°C)* 体外 DMSO 58 mg/mL (198.37 mM)
Ethanol 8 mg/mL (27.36 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
30%propylene glycol 5%Tween80 65%D5W
30.0mg/ml Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified propylene glycol stock solution to 50 μL of Tween 80, mix evenly to clarify it; then continue to add 650 μL of D5W to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 RITA 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.
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]
特徴 Inducer of DNA cross-links, not a DNA intercalator.

プロトコル(参考用のみ)

細胞アッセイ 細胞株 HCT116 cells and HCT116 TP53-/- cells
濃度 0.1 nM - 1 mM, 10 mM stocked in DMSO
反応時間 48 hours
実験の流れ 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
動物実験 動物モデル SCID mice carrying HCT116 and HCT116 TP53-/- xenografts
投薬量 0.1 mg/kg, 1 mg/kg or 10 mg/kg
投与方法 Administered via i.v. or i.p.

カスタマーフィードバック

Data from [Data independently produced by Oncogene, 2014, 10.1038/onc.2014.37]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Tripartite motif containing 69 elicits ERK2-dependent EYA4 turnover to impart pancreatic tumorigenesis [ J Cancer, 2023, 14(2):200-218] PubMed: 36741265
Wnt4 is crucial for cardiac repair by regulating mesenchymal-endothelial transition via the phospho-JNK/JNK [ Theranostics, 2022, 12(9):4110-4126] PubMed: 35673578
Mild oxidative stress protects against chemotherapy-induced hair loss [ Front Oncol, 2022, 12:1078916] PubMed: 36703797
Arsenic Trioxide Rescues Structural p53 Mutations through a Cryptic Allosteric Site [ Cancer Cell, 2020, S1535-6108(20)30605-X] PubMed: 33357454
The Meningioma Enhancer Landscape Delineates Novel Subgroups and Drives Druggable Dependencies [ Cancer Discov, 2020, CD-20-0160] PubMed: 32703768
A Human Organoid Model of Aggressive Hepatoblastoma for Disease Modeling and Drug Testing [ Cancers (Basel), 2020, 12(9)E2668] PubMed: 32962010
Wild-Type p53 Promotes Cancer Metabolic Switch by Inducing PUMA-Dependent Suppression of Oxidative Phosphorylation [ Cancer Cell, 2019, 35(2):191-203] PubMed: 30712844
Angiopoietin-like protein 3 blocks nuclear import of FAK and contributes to sorafenib response. [ Br J Cancer, 2018, 119(4):450-461] PubMed: 30033448
Identification of differentially expressed genes associated with the enhancement of X-ray susceptibility by RITA in a hypopharyngeal squamous cell carcinoma cell line (FaDu). [ Radiol Oncol, 2016, 50(2):168-74] PubMed: 27247549
Correlating chemical sensitivity and basal gene expression reveals mechanism of action [Rees MG, et al. Nat Chem Biol, 2015, 10.1038/nchembio.1986] PubMed: 26656090

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人間や獣医の診断であるか治療的な使用のためにでない。

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