RITA (NSC 652287)

貨號 Cat. No.: S2781
規格 Size: 5~200mg
品牌 Brand: Selleckchem

Description

RITA (NSC 652287)

Catalog No.S2781

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.

Size

Price

Stock

Quantity

10mM/1mLIn DMSO	USD 252	In stock	0 1 2 3 4 5 6 7 8 9 10
5mg	USD 214	In stock	0 1 2 3 4 5 6 7 8 9 10
10mg	USD 340	In stock	0 1 2 3 4 5 6 7 8 9 10
50mg	USD 1348	In stock	0 1 2 3 4 5 6 7 8 9 10

Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw

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.
Targets	DNA cross-links (A498 cells)	DNA cross-links (TK-10 cells)
IC50	2 nM	20 nM ^[1]
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]
Features	Inducer of DNA cross-links, not a DNA intercalator.

Protocol(Only for Reference)

Cell Assay: ^[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 Study: ^[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	30% propylene glycol, 5% Tween 80, 65% D5W, 30 mg/mL

References

Clinical Trial Information( data from http://clinicaltrials.gov)

NCT Number	Recruitment	Conditions	Sponsor /Collaborators	Start Date	Phases
NCT01834625	Recruiting	Normal Pressure Hydrocephalus Patients	Mayo Clinic	2013-04	Phase 0
NCT01860430	Recruiting	Cancer of Head and Neck	University of Pittsburgh\|National Cancer Institute (NCI)	2013-04	Phase 1
NCT01641107	Not yet recruiting	Philadelphia Positive\|BCR-ABL Positive\|Acute Lymphoblastic Leukemia	Gruppo Italiano Malattie EMatologiche dell’Adulto	2013-04	Phase 2
NCT01831180	Not yet recruiting	Healthy	Wake Forest University\|Procter and Gamble	2013-05
NCT01699217	Not yet recruiting	Chronic Phase Philadelphia Positive\|BCR-ABL Positive\|Chronic Myeloid Leukaemia	Gruppo Italiano Malattie EMatologiche dell’Adulto	2013-07

Chemical Information

Download RITA (NSC 652287) SDF

Molecular Weight (MW)	292.37
Formula	C₁₄H₁₂O₃S₂
CAS No.	213261-59-7

Storage	3 years -20â„ƒPowder
Storage	6 months-80â„ƒin DMSO
Syonnyms	SOS BISMETHANOL

Solubility (25°C) *	In vitro	DMSO	58 mg/mL (198 mM)
		Water	<1 mg/mL (<1 mM)
		Ethanol	8 mg/mL (27 mM)
	In vivo	30% propylene glycol, 5% Tween 80, 65% D5W,	30 mg/mL
* <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.