生物活性

• 描述RITA (NSC 652287), a representative of a series of thiophene derivatives, is a DNA damage inducing agent that induces both DNA-protein and DNA-DNA cross-links with no detectable DNA single-strand breaks and exhibits potent and selective antitumor activity against several tumor cell lines^[3]. The renal carcinoma cell line A498 treated with 10 nM NSC 652287 exhibited cell cycle arrest in G(0)-G(1) and G(2)-M, with increased p53 and p21(WAF1) protein. NSC 652287 at higher concentrations still induced p53 elevation but with p21(WAF1) reduction and massive apoptosis^[3]. MCF-7 and MDA-MB-231 cells were treated with RITA (1 μM) for 24 h in normoxia and hypoxia (1% O2) and there was a clear increase in rounding and displacement of cells from monolayers in tissue culture, indicative of apoptosis, to a similar extent in normoxia and hypoxia^[4]. RITA exhibits potent antileukemic properties against p53-null chronic myeloid leukemia (CML)-derived K562 cells by triggering apoptosis through caspase-9 and caspase-3 activation and poly (ADP-ribose) polymerase cleavage, in a dose- and time-dependent manner (1,2 and 4 µM)^[5].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00232648	Asthma	Phase 3	Completed	-	Japan ... more >> Fukuoka-City, Fukuoka, Japan Isehara-City, Kanagawa, Japan Tsu-City, Mie, Japan Kurashiki City, Okayama, Japan Hioshima, Japan Kanagawa, Japan Matsuyama City, Japan Obhu-city, Japan Tokyo, Japan Collapse <<
  NCT01062633	Dental Caries	Phase 2 Phase 3	Unknown	November 2011	Estonia ... more >> Department of Stomatology, University of Tartu Recruiting Tartu, Estonia, 51003 Contact: Mare Saag, PhD    +372 7 319 855    mare.saag@ut.ee    Contact: Rita Nommela, PhD    +372 7 319 860    rita.nommela@ut.ee    Sub-Investigator: Jana Olak, DDS          Sub-Investigator: Riina Runnel, DDS          Sub-Investigator: Pirkko-Liisa Makinen, PhD          Sub-Investigator: Sisko Honkala, PhD          Sub-Investigator: Rita Nommela, PhD          Sub-Investigator: Silvia Russsak, PhD Collapse <<
  NCT01639235	-	-	Recruiting	August 2020	United States, California ... more >> University of California, San Francisco (UCSF) Recruiting San Francisco, California, United States, 94143 Contact: Paula Tarr    415-502-2345    Paula.Tarr@ucsf.edu    Principal Investigator: Rita Redberg, MD          Sub-Investigator: Eveline Stock, MD Collapse <<

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• 参考文献

• [1] Roh JL, Ko JH, et al. The p53-reactivating small-molecule RITA enhances cisplatin-induced cytotoxicity and apoptosis in head and neck cancer. Cancer Lett. 2012 Dec 1;325(1):35-41.

  [2] Rivera MI, Stinson SF, et al. Selective toxicity of the tricyclic thiophene NSC 652287 in renal carcinoma cell lines: differential accumulation and metabolism. Biochem Pharmacol. 1999 Jun 1;57(11):1283-95.

  [3] Nieves-Neira W, Rivera MI, Kohlhagen G, Hursey ML, Pourquier P, Sausville EA, Pommier Y. 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. doi: 10.1124/mol.56.3.478. PMID: 10462535.

  [4] Yang J, Ahmed A, Poon E, Perusinghe N, de Haven Brandon A, Box G, Valenti M, Eccles S, Rouschop K, Wouters B, Ashcroft M. Small-molecule activation of p53 blocks hypoxia-inducible factor 1alpha and vascular endothelial growth factor expression in vivo and leads to tumor cell apoptosis in normoxia and hypoxia. Mol Cell Biol. 2009 Apr;29(8):2243-53. doi: 10.1128/MCB.00959-08. Epub 2009 Feb 17. PMID: 19223463; PMCID: PMC2663300.

  [5] Mobaraki RN, Karimi M, Alikarami F, Farhadi E, Amini A, Bashash D, Paridar M, Kokhaei P, Rezvani MR, Kazemi A, Safa M. RITA induces apoptosis in p53-null K562 leukemia cells by inhibiting STAT5, Akt, and NF-κB signaling pathways. Anticancer Drugs. 2018 Oct;29(9):847-853. doi: 10.1097/CAD.0000000000000651. PMID: 30157040.

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