RITA (NSC 652287)

Names

[ Name ]:
RITA (NSC 652287)

[Synonym ]:
p53 Activator III,RITA
(Furan-2,5-diyldithiene-5,2-diyl)dimethanol
RITA
(2,5-Furandiyldi-5,2-thienediyl)dimethanol
2-Thiophenemethanol, 5,5'-(2,5-furandiyl)bis-
SOS BISMETHANOL
Reactivation of p53 and Induction of Tumor cell Apoptosis
NSC 652287
5,5'-(2,5-Furandiyl)bis-2-thiophenemethanol
NSC652287

Biological Activity

[Description]:

RITA is an inhibitor of p53-HDM-2 interaction, binds to p53dN, with a Kd of 1.5 nM, and also induces DNA-DNA cross-links.

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA Alkylator/Crosslinker

Signaling Pathways >> Apoptosis >> MDM-2/p53

Research Areas >> Cancer

[Target]

Kd: 1.5 nM (p53dN)[1] DNA Crosslinker[2]

[In Vitro]

RITA inhibits p53-HDM-2 interaction, binding to p53dN, with a Kd of 1.5 nM. RITA (10 μM) blocks complex formation between p53 and HDM-2 in HCT116 cells and HDFs and in NHF-ERMyc cells irrespective of c-Myc expression. RITA (0.5 μM) reduces the viability of tumor cells in a wild-type p53-dependent manner. Moreover, RITA (0.1 μM) induces p53-dependent apoptosis. RITA induces p53 but does not via DNA damage-signaling pathway[1]. RITA (NSC 652287) induces DNA-DNA cross-links. RITA induces G2-M cell cycle arrest at 10 nM and causes apoptosis at 100 nM. RITA (100 nM) also elevates p53 and causes dose-dependent effects on p21WAF1 protein levels[2]. RITA inhibits the growth of HeLa and CaSki cells, with IC50s of 1 and 10 μM. In addition, RITA (1 μM) stabilizes p53 by inhibiting p53/E6AP interaction[3].

[In Vivo]

RITA (0.1, 1 or 10 mg/kg, i.p.) shows potent antitumor activity in SCID mice bearing HCT116 and HCT116 TP53−/− xenografts[1]. RITA (10 mg/kg, i.p.) also suppresses the growth of HeLa cells in SCID mice[3].

[Cell Assay]

For the cell viability assay, 3,000 cells per well are plated in a 96-well plate and treated with RITA for 48 h, after which cell viability is assessed with the proliferation reagent WST-1. For colony formation assay, cells are seeded in 12-well plates and treated with RITA for 24 h, after which the medium is replaced and the cells are allowed to grow for 10-14 d. The colonies are stained with crystal violet. For growth curves, 3000 cells/mL are plated in 12-well plates, treated with RITA, and counted over 5 d[3].

[Animal admin]

Mice[1] Female SCID mice, 4-6 weeks old, are implanted with subcutaneous xenografts using 1 × 106 cells in 90% Matrigel. Palpable tumors are established 3-6 d after the cells are injected, at which point RITA treatment is initiated. RITA is administered either 0.1, 1 or 10 mg/kg every day by intravenous or intraperitoneal injection in a total volume of 100 μL phosphate buffered saline. Xenografts are measured every 2 d. Tumor volumes are plotted for control and treated groups by dividing the average tumor volume for each data point by average starting tumor volume[1].

[References]

[1]. Issaeva N, et al. Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors. Nat Med. 2004 Dec;10(12):1321-8. Epub 2004 Nov 21.

[2]. Nieves-Neira W, et al. DNA protein cross-links produced by NSC 652287, a novel thiophene derivative active against human renal cancer cells. Mol Pharmacol. 1999 Sep;56(3):478-84.

[3]. Zhao CY, et al. Rescue of p53 function by small-molecule RITA in cervical carcinoma by blocking E6-mediated degradation. Cancer Res. 2010 Apr 15;70(8):3372-81.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
464.9±40.0 °C at 760 mmHg

[ Melting Point ]:
160 °C

[ Molecular Formula ]:
C₁₄H₁₂O₃S₂

[ Molecular Weight ]:
292.373

[ Flash Point ]:
235.0±27.3 °C

[ Exact Mass ]:
292.022797

[ PSA ]:
110.08000

[ LogP ]:
2.48

[ Vapour Pressure ]:
0.0±1.2 mmHg at 25°C

[ Index of Refraction ]:
1.661

[ Storage condition ]:
Store at -20°C

Safety Information

[ Hazard Codes ]:
Xi

RITA (NSC 652287)

Names

Biological Activity

Chemical & Physical Properties

Safety Information

Related Compounds