RITA

製品コードS2781 バッチS278101

印刷

化学情報

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）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	30%propylene glycol 1 5%Tween80 2 65%D5W この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	30.000mg/ml (102.61mM)	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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	0.500mg/ml (1.71mM)	Taking the 1 mL working solution as an example, add 50 μL of 10 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O 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. This compound also inhibits the growth of other renal cell lines including ACHN and UO-31 with IC50 of 13 μM and 37 μM, respectively. ^[1] It (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. This chemical (30 nM) also induces both DNA-protein and DNA-DNA cross-links in A498 cells. Meanwhile it has no effects on top1-mediated relaxation of supercoiled SV40 DNA. ^[2] It significantly suppresses the growth of HCT116 cells (97%) but only slightly inhibits the growth of HCT116 TP53^-/- cells (13%). This compound 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. It 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). This chemical blocks p53−HDM-2 interaction and p53 ubiquitination. It substantially decreases the amount of HDM-2 that is co-precipitated with p53, although both proteins are upregulated. This compound prevents interactions between the purified GST-p53 and 6XHis-tagged His-HDM-2 proteins. ^[3] It is shown to induce apoptosis by promoting p53Ser46 phosphorylation. ^[4] This chemical induces activation of p53 in conjunction with up-regulation of phosphorylated ASK-1, MKK-4 and c-Jun. It induces the activation of JNK signaling. ^[5] But On the contrary, another results by nuclear magnetic resonance (NMR) show that it 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 this compound 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 this compound, 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, it shows strong antitumor activity. Five 1 mg/kg injections of this chemical 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 it than in control untreated mice. This compound 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 this compound in DMSO are added to the wells, and sensitivity is determined 48 hours after the addition of this chemical.
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.

参考

https://pubmed.ncbi.nlm.nih.gov/10230772/
https://pubmed.ncbi.nlm.nih.gov/10462535/
https://pubmed.ncbi.nlm.nih.gov/15558054/

https://pubmed.ncbi.nlm.nih.gov/22166212/
https://pubmed.ncbi.nlm.nih.gov/22276160/
https://pubmed.ncbi.nlm.nih.gov/16270059/

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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：

Tert promotes cardiac regenerative repair after MI through alleviating ROS-induced DNA damage response in cardiomyocyte [ Cell Death Discov, 2024, 10(1):381]	PubMed: 39187478
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
Tubule-specific deletion of LincRNA-p21ameliorates lipotoxic kidney injury [ Mol Ther Nucleic Acids, 2021, 26:1280-1290]	PubMed: 34853727
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

長期の保管のために-20°Cの下で製品を保ってください。

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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