213261-59-7

Basic information

• Product Name: 5,5'-(2,5-FURANDIYL)BIS-2-THIOPHENEMETHANOL
• Synonyms: 5,5'-(2,5-FURANDIYL)BIS-2-THIOPHENEMETHANOL;RITA;p53 Activator III;RITA (NSC 652287);(5,5'-(furan-2,5-diyl)bis(thiophene-5,2-diyl))diMethanol;RITA, >99%;2-Thiophenemethanol, 5,5'-(2,5-furandiyl)bis-;5,5'-(2,5-Furandiyl)bis-2-thiophenemethanol RITA (NSC 652287)
• CAS NO: 213261-59-7
• Molecular Formula: C14H12O3S2
• Molecular Weight: 292.37328
• EINECS: 200-256-5
• Product Categories: Inhibitor;Inhibitors
• Mol File: 213261-59-7.mol

Chemical Properties

• Melting Point: 160 °C
• Boiling Point: 464.9°Cat760mmHg
• Flash Point: 235°C
• Appearance: /
• Density: 1.396g/cm³
• Vapor Pressure: 1.92E-09mmHg at 25°C
• Refractive Index: 1.661
• Storage Temp.: Store at -20°C
• Solubility: Soluble in DMSO (up to 20 mg/ml)
• PKA: 13.43±0.10(Predicted)
• Sensitive: Light Sensitive
• Stability: Stable for 2 years as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: 5,5'-(2,5-FURANDIYL)BIS-2-THIOPHENEMETHANOL(CAS DataBase Reference)
• NIST Chemistry Reference: 5,5'-(2,5-FURANDIYL)BIS-2-THIOPHENEMETHANOL(213261-59-7)
• EPA Substance Registry System: 5,5'-(2,5-FURANDIYL)BIS-2-THIOPHENEMETHANOL(213261-59-7)

Safety Data

• Hazardous Substances Data: 213261-59-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
5,5'-(2,5-FURANDIYL)BIS-2-THIOPHENEMETHANOL is used as a DNA damaging agent for its ability to induce the p53 tumor suppressor protein, which is essential in preventing cancer development. Its role in changing the conformation of p53 and preventing its degradation makes it a promising candidate for cancer therapeutics.
Used in Cancer Research:
As a p53-targeting compound, 5,5'-(2,5-FURANDIYL)BIS-2-THIOPHENEMETHANOL is utilized in cancer research to study the mechanisms of p53 regulation and its role in tumor suppression. Its ability to restore mutant p53 function and induce apoptosis via various pathways makes it a valuable tool for understanding cancer cell biology and developing novel therapeutic strategies.
Used in Drug Development:
5,5'-(2,5-FURANDIYL)BIS-2-THIOPHENEMETHANOL serves as a starting point for the development of new drugs targeting p53 and HDM2 interactions. Its unique properties and mechanisms of action can be leveraged to design more effective and targeted cancer therapies, potentially leading to improved treatment outcomes for patients.
Used in Combination Therapies:
5,5'-(2,5-FURANDIYL)BIS-2-THIOPHENEMETHANOL demonstrates potential for use in combination therapies, as it can enhance the chemo-sensitivity and efficacy of conventional chemotherapeutic drugs in resistant cases. Its synergistic anticancer effects make it a valuable candidate for combination treatments, aiming to improve overall cancer treatment success rates.
Used in Drug Delivery Systems:
To overcome potential limitations of 5,5'-(2,5-FURANDIYL)BIS-2-THIOPHENEMETHANOL, such as bioavailability and delivery issues, novel drug delivery systems are being developed. These systems, including organic and metallic nanoparticles, aim to improve the compound's delivery, bioavailability, and therapeutic outcomes in cancer treatment.

Biological Activity

Anti-tumor agent that binds wild-type p53 (K d = 1.5 nM) preventing p53-MDM2 (HDM2) interaction. Induces p53 accumulation and stimulates apoptosis in tumor cell lines expressing wild-type p53 in vitro and in vivo .

in vitro

a number of cell lines showed a striking differential sensitivity to nsc 652287 when compared with the other cell lines in the panel, with gi50 values of 10–60 nm. the compound was found to decrease the initial number of cells by 50% (lc50) at a concentration of 100 nm in the a-498 cell line, compared with ~100 mm for the majority of the tumor cell lines. the a-498 and tk-10 cell lines were particularly sensitive to nsc 652287-induced cytotoxicity compared with achn and uo-31 cell lines [1].

in vivo

nsc 652287 was evaluated against a-498 tumor cell xenografts grown subcutaneously in nude mice. when nsc 652287 was administered twice a day, all three doses resulted in complete tumor regression in 100% of the treated mice by the end of the third treatment period. the tumors did not regrow during the remaining 40 days of the study, and no gross evidence of toxicity was observed. studies with xenografts derived from other sensitive cell lines including the renal caki-1, melanoma uacc-257, ovarian ovcar-5, and colon hcc-2998, showed moderate or minimal in vivo activity [2].

IC 50

2 nm and 20 nm for a-498 and tk-10, respectively

References

Issaeva et al. (2004), Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors; Nat. Med., 10 1321 Espinoza-Fonseca et al. (2005), Targeting MDM2 by the small molecule RITA: towards the development of new multi-target drugs against cancer; Theor. Biol. Med. Model, 2 38 Ristau et al. (2019), RITA requires eIF2α-dependent modulation of mRNA translation for its anti-cancer activity; Cell Death Dis., 10 845 Zhao et al. (2010), Rescue of the apoptotic-inducing function of mutant p53 by small molecule RITA; Cell Cycle, 9 1847 Weilbacher et al. (2014), RITA can induce cell death in p53-defective cells independently of p53 function via activation of JNK/SAPK and p38; Cell Death Dis., 5 e1318 Chuang et al. (2014), The p53-reactivating small molecule RITA induces senescence in head and neck cancer cells.; PLoS One, 9(8) e104821

InChI:InChI=1/C14H12O3S2/c15-7-9-1-5-13(18-9)11-3-4-12(17-11)14-6-2-10(8-16)19-14/h1-6,15-16H,7-8H2

Upstream product

• 868755-64-0 5-(furan-2-yl)thiophene-2-carboxaldehyde 
• 4701-17-1 5-bromo-2-thiophencarboxaldehyde 
• 443095-23-6 C₁₄H₁₀O₃S₂ 
• 1415721-03-7 (5-(5-bromofuran-2-yl)thiophen-2-yl)methanol 
• 1375927-88-0 5-(5-bromofuran-2-yl)thiophene-2-carbaldehyde 

Relevant articles and documents

Synthesis and antiproliferative activity of RITA and its analogs

The synthesis of RITA and a variety of five-membered heterocyclic triads by the cyclocondensation of 1,4-bis(5-substituted-2-thienyl or 2-furyl)-1,3-butadiynes with water or Na2S·9H2O in the presence of KOH in DMSO is described. The study on the antiproliferative activities against K562, MCF-7, A549, and HCT116 tumor cells has revealed that some of the heterocyclic triads show higher antiproliferative activities than RITA, depending on the structures of substituents, the property of heteroatoms as well as their numbers.

Efficient synthesis of RITA and its analogues: Derivation of analogues with improved antiproliferative activity via modulation of p53/miR-34a pathway

A novel approach to synthesize RITA by practical palladium-catalyzed C-C bond-forming Suzuki reactions at room temperature was developed, which was used for deriving a series of substituted tricyclic α-heteroaryl (furan/thiophene) analogues of RITA under mild conditions. These novel analogues showed notable antiproliferative activity against cancer cell lines with wild-type p53 (i.e., HCT116, A549, MCF-7 and K562), but much less activity in HCT116/p53-/- cells. In particular, compound 1f demonstrated promising antiproliferative activity compared to RITA, with IC50 = 28 nM in MCF-7 vs. 54 nM for RITA, and cancer cell selectivity. Compound 1f markedly activated p53 in HCT116 cells at 100 nM, triggering apoptosis. Importantly, we found that both RITA and compound 1f induced G 0/G1 cell cycle arrest by up-regulating miR-34a, which in turn down-regulated the expression of cell cycle-related proteins CDK4 and E2F1. In summary, this study reports an effective synthetic approach for RITA and its analogues, and elucidates a novel antiproliferative mechanism of these compounds. The Royal Society of Chemistry 2012.