Deferasirox
(Synonyms: 地拉罗司; ICL 670) 目录号 : GC11835
Deferasirox是一种具口服活性的铁螯合剂，用于治疗铁过载疾病。
Cas No.:201530-41-8
Sample solution is provided at 25 µL, 10mM.
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Deferasirox is an orally active iron chelator used to treat iron overload diseases[1]. Deferasirox belongs to the family of N-substituted bishydroxyphenyltriazole tridentate iron chelators with antitumor activity[2]. Deferasirox is a potent nuclear factor-κB (NF-κB) inhibitor whose mechanism of action is independent of chelation-induced cellular iron deprivation[3].
In vitro, treatment of esophageal cancer OE33, OE19, and OE21 cells with Deferasirox (20μM) for 48h significantly increased transferrin receptor 1 (TfR1) mRNA and protein expression in the three cell lines, resulting in decreased cell viability and proliferation[4]. Treatment of LX-2 stellate cells with Deferasirox (50μM) for 12h significantly reduced the expression of α1(I) procollagen and α-smooth muscle actin (αSMA)[5].
In vivo, oral administration of Deferasirox (20mg/kg) to mice with secondary iron overload (SIO) inoculated with L1210 cells prolonged survival, reduced tumor volume, and decreased iron content in liver or tumor tissues[6]. Oral administration of Deferasirox (25mg/kg) to rats with iron poisoning significantly improved serum biochemical parameters[7].
References:
[1] Choudhry V P, Naithani R. Current status of iron overload and chelation with deferasirox[J]. The Indian Journal of Pediatrics, 2007, 74: 759-764.
[2] Barani M, Sargazi S, Hajinezhad M R, et al. Preparation of pH-responsive vesicular deferasirox: Evidence from in silico, in vitro, and in vivo evaluations[J]. ACS omega, 2021, 6(37): 24218-24232.
[3] Messa E, Carturan S, Maffè C, et al. Deferasirox is a powerful NF-κB inhibitor in myelodysplastic cells and in leukemia cell lines acting independently from cell iron deprivation by chelation and reactive oxygen species scavenging[J]. Haematologica, 2010, 95(8): 1308.
[4] Ford S J, Obeidy P, Lovejoy D B, et al. Deferasirox (ICL670A) effectively inhibits oesophageal cancer growth in vitro and in vivo[J]. British journal of pharmacology, 2013, 168(6): 1316-1328.
[5] Sobbe A, Bridle K R, Jaskowski L, et al. Inconsistent hepatic antifibrotic effects with the iron chelator deferasirox[J]. Journal of Gastroenterology and Hepatology, 2015, 30(3): 638-645.
[6] Lee D H, Jang P S, Chung N G, et al. Deferasirox shows in vitro and in vivo antileukemic effects on murine leukemic cell lines regardless of iron status[J]. Experimental Hematology, 2013, 41(6): 539-546.
[7] Rahdar A, Hajinezhad M R, Sargazi S, et al. Biochemical effects of deferasirox and deferasirox-loaded nanomicellesin iron-intoxicated rats[J]. Life Sciences, 2021, 270: 119146.
Deferasirox是一种具口服活性的铁螯合剂，用于治疗铁过载疾病[1]。Deferasirox属于N取代的双羟基苯基三唑三齿铁螯合剂家族，具有抗肿瘤活性[2]。Deferasirox是一种有效的核因子-κB（NF-κB）抑制剂，其作用机制独立于螯合引起的细胞铁剥夺[3]。
在体外，Deferasirox（20μM）处理食管癌OE33、OE19、OE21细胞48h，显著增加了三种细胞系中转铁蛋白受体1（TfR1）mRNA和蛋白质表达，导致了细胞活力降低和增殖减少[4]。Deferasirox（50μM）处理LX-2星状细胞12h，显著降低了α1（I）前胶原和α-平滑肌肌动蛋白（αSMA）的表达[5]。
在体内，Deferasirox（20mg/kg）通过口服治疗接种L1210细胞的继发性铁过载（SIO）小鼠，延长了生存期，减小了肿瘤体积，降低了肝脏或肿瘤组织的铁含量[6]。Deferasirox（25mg/kg）通过口服治疗铁中毒大鼠，显著提高了大鼠的血清生化参数[7]。
| Cell experiment [1]: | |
Cell lines | OE33, OE19, OE21 cells |
Preparation Method | All three oesophageal cell lines, OE33, OE19 and OE21, were incubated with Deferasirox (20μM) or Deferoxamine (10μM) for 48h/37°C. qRT-PCR was employed to assess levels of TfR1, ferritin-H and FPN mRNA relative to control cells. In addition, protein lysates were subject to Western blotting to assess protein levels of TfR1, ferritin-H and FPN. |
Reaction Conditions | 20μM; 48h |
Applications | Deferasirox treatment resulted in a significant increase in TfR1 mRNA and protein expression in all cell lines. Deferasirox treatment did not significantly alter ferritin-H mRNA and protein levels and FPN mRNA. |
| Animal experiment [2]: | |
Animal models | Non-SIO mice and secondary iron overload (SIO) mice bearing L1210 cells |
Preparation Method | Murine leukemia cells (L1210) were harvested, and 2×106 cells were injected subcutaneously into the right flank of mice anesthetized with 0.4% Avertin. After engraftment, the tumor size was measured three times per week with Vernier calipers. When tumor mass reaches visible size, the Deferoxamine group was given Deferoxamine (40mg/kg/day, i.p.) for 6 consecutive days, and the Deferasirox group was given Deferasirox (20mg/kg/day dissolved in 200mL distilled water, orally) until the cumulative dose reached 300mg/kg. The mice were observed and weighed daily. Liver and tumor tissues were collected immediately after death and preserved at -80℃ until iron content analysis was performed. The iron content of the liver and tumor tissues were measured using an atomic absorption spectrophotometer. |
Dosage form | 20mg/kg/day; p.o. |
Applications | The non-SIO mice and SIO mice bearing L1210 cells showed longer survival than other groups when treated with Deferasirox. The tumor was significantly smaller in the SIO mice treated with Deferasirox compared with the control group, the iron content of the liver or the tumor was decreased. |
References: | |
| Cas No. | 201530-41-8 | SDF | |
| 别名 | 地拉罗司; ICL 670 | ||
| 化学名 | 4-[(3Z,5E)-3,5-bis(6-oxocyclohexa-2,4-dien-1-ylidene)-1,2,4-triazolidin-1-yl]benzoic acid | ||
| Canonical SMILES | C1=CC(=C2NC(=C3C=CC=CC3=O)N(N2)C4=CC=C(C=C4)C(=O)O)C(=O)C=C1 | ||
| 分子式 | C21H15N3O4 | 分子量 | 373.36 |
| 溶解度 | ≥100 mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6784 mL | 13.3919 mL | 26.7838 mL |
| 5 mM | 0.5357 mL | 2.6784 mL | 5.3568 mL |
| 10 mM | 0.2678 mL | 1.3392 mL | 2.6784 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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