Deferoxamine mesylate
(Synonyms: 甲磺酸去铁胺; Desferrioxamine B mesylate; DFOM) 目录号 : GC13554
An iron chelator and inhibitor of prolyl hydroxylases
Cas No.:138-14-7
Sample solution is provided at 25 µL, 10mM.
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- Purity: >99.00%
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| Cell experiment [1]: | |
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Cell lines |
RPE cells, 4 or 24h |
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Preparation Method |
Subconfluent RPE cells were stimulated for 4 hours or 24 hours with 0µM, 100µM, 260µM, or 500µM of deferoxamine mesylate suspended in sterile distilled water. |
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Reaction Conditions |
0µM, 100µM, 260µM, or 500µM deferoxamine mesylate |
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Applications |
Deferoxamine mesylate induces significant cell death compared with untreated controls in the RPE cells when treated for 4 hours or 24 hours with 260µM and 500µM, but not when treated with 100µM, of deferoxamine. |
| Animal experiment [2]: | |
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Animal models |
Male Sprague-Dawley rats, 180-200g |
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Preparation Method |
Rats were either iron depleted by daily injections of 200mg/kg deferoxamine mesylate (Novartis)37 or submitted to injections of solvent (0.9% saline), for 2 weeks. |
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Dosage form |
200mg/kg deferoxamine mesylate |
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Applications |
Iron depletion by deferoxamine mesylate affects glucose metabolism inducing glucose uptake and utilization and increasing InsR binding activity and signaling, and that the mechanism is associated with HIF-1 stabilization and requires the presence of HIF-1/ARNT. |
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References: [1]. Klettner A, Koinzer S, et al. Deferoxamine mesylate is toxic for retinal pigment epithelium cells in vitro, and its toxicity is mediated by p38. Cutan Ocul Toxicol. 2010;29(2):122-129. [2]. Dongiovanni P, Valenti L, et al. Iron depletion by deferoxamine up-regulates glucose uptake and insulin signaling in hepatoma cells and in rat liver. Am J Pathol. 2008;172(3):738-747. |
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Deferoxamine mesylate is a drug that chelates iron by forming a stable complex that prevents the iron from entering into further chemical reactions, and is used for the treatment of chronic iron overload in patients with transfusion-dependent anemias[1,2].
Deferoxamine mesylate (260μM) is directly toxic on RPE cells, its toxicity depending on p38[1]. Deferoxamine mesylate administration resulted in reduced cytotoxicity and ROS generation by Fe(Salen) in Rabbit squamous cell carcinoma (VX2) cells, human glioblastoma malignant glioma cells (YKG)OVK18, and human ovarian carcinoma cells[3]. Deferoxamine mesylate (30μM) significantly inhibits the growth of human hepatocellular carcinoma and hepatoblastoma cell lines[4].
Deferoxamine mesylate enhances urinary iron elimination and decreases hepatic iron accumulation after blood transfusion in foals[2]. Deferoxamine mesylate (25mg/kg, intravenous injection) reduced the onset of Fe (Salen) (25mg/kg)-induced acute liver and renal dysfunction. Deferoxamine mesylate (300mg/kg) improves survival rate after systematic injection of a fatal dose of Fe (Salen) (200mg/kg) in Male ICR[3]. Use of deferoxamine mesylate in bone defects promotes vascularization and osteogenesis in the defect area, and maintains the protein activity of HIF-1α temporarily[5]. Deferoxamine mesylate can ameliorate tissue ischemia-reperfusion injury. Deferoxamine mesylate preconditioning protected pancreatic tissue in orthotopic liver autotransplantation in rats[6].
References:
[1] Klettner A, Koinzer S, et al. Deferoxamine mesylate is toxic for retinal pigment epithelium cells in vitro, and its toxicity is mediated by p38. Cutan Ocul Toxicol. 2010;29(2):122-129.
[2] Elfenbein JR, Giguère S, et al. The effects of deferoxamine mesylate on iron elimination after blood transfusion in neonatal foals. J Vet Intern Med. 2010;24(6):1475-1482.
[3] Umemura M, Kim JH, et al. The iron chelating agent, deferoxamine detoxifies Fe(Salen)-induced cytotoxicity. J Pharmacol Sci. 2017;134(4):203-210.
[4] Tabor E, Kim CM. Inhibition of human hepatocellular carcinoma and hepatoblastoma cell lines by deferoxamine. J Med Virol. 1991;34(1):45-50.
[5]DU WY, Yang JW, et al. [Early constant observation of the effect of deferoxamine mesylate on improvement of vascularized bone regeneration in SD rat skull critical size defect model]. Beijing Da Xue Xue Bao Yi Xue Ban. 2021 Dec 18;53(6):1171-1177. Chinese.
[6]Li Y, Zhang PJ, et al. Protective effects of deferoxamine mesylate preconditioning on pancreatic tissue in orthotopic liver autotransplantation in rats. Transplant Proc. 2011;43(5):1450-1455.
Deferoxamine mesylate 是一种通过形成稳定的复合物来螯合铁的药物，该复合物可防止铁进入进一步的化学反应，并用于治疗输血依赖性贫血患者的慢性铁过载[1, 2].
Deferoxamine mesylate (260μM) 对 RPE 细胞有直接毒性，其毒性取决于 p38[1]。施用甲磺酸去铁胺可降低兔鳞状细胞癌 (VX2) 细胞、人胶质母细胞瘤恶性胶质瘤细胞 (YKG)OVK18 和人卵巢癌细胞中 Fe(Salen) 的细胞毒性和 ROS 生成[3] . Deferoxamine mesylate (30μM)显着抑制人肝细胞癌和肝母细胞瘤细胞系的生长[4]。
甲磺酸去铁胺增强马驹输血后尿液铁的消除并减少肝脏铁的积累[2]。 Deferoxamine mesylate (25mg/kg, 静脉注射)减少了Fe (Salen) (25mg/kg)诱导的急性肝肾功能障碍的发生。甲磺酸去铁胺 (300mg/kg) 在男性 ICR[3] 中系统注射致命剂量的 Fe (Salen) (200mg/kg) 后提高了存活率。甲磺酸去铁胺在骨缺损中的应用促进了缺损区域的血管形成和成骨，并暂时维持了HIF-1α的蛋白活性[5]。 Deferoxamine mesylate 可以改善组织缺血再灌注损伤。甲磺酸去铁胺预处理对大鼠原位自体肝移植胰腺组织的保护作用[6].
| Cas No. | 138-14-7 | SDF | |
| 别名 | 甲磺酸去铁胺; Desferrioxamine B mesylate; DFOM | ||
| 化学名 | (Z)-4-((5-aminopentyl)(hydroxy)amino)-N-(5-((Z)-N,4-dihydroxy-4-((5-(N-hydroxyacetamido)pentyl)imino)butanamido)pentyl)-4-oxobutanimidic acid compound with methanesulfonic acid (1:1) | ||
| Canonical SMILES | CC(N(O)CCCCC/N=C(O)/CCC(N(O)CCCCC/N=C(O)/CCC(N(O)CCCCCN)=O)=O)=O.CS(O)(=O)=O | ||
| 分子式 | C26H52N6O11S | 分子量 | 656.79 |
| 溶解度 | ≥ 65.7mg/mL in Water | 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.5226 mL | 7.6128 mL | 15.2256 mL |
| 5 mM | 0.3045 mL | 1.5226 mL | 3.0451 mL |
| 10 mM | 0.1523 mL | 0.7613 mL | 1.5226 mL |
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| 给药剂量 | mg/kg |  |
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；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
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2.
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Deferoxamine mesylate: a new hope for intracerebral hemorrhage: from bench to clinical trials
Iron resulting from hemoglobin degradation is linked to delayed neuronal injury after intracerebral hemorrhage. Extensive preclinical investigations indicate that the iron chelator, deferoxamine mesylate, is effective in limiting hemoglobin- and iron-mediated neurotoxicity. However, clinical studies evaluating the use of deferoxamine in intracerebral hemorrhage are shortcoming. This article reviews the potential role of deferoxamine as a promising neuroprotective agent to target the secondary effects of intracerebral hemorrhage to limit brain injury and improve outcome, and ongoing efforts to translate the preclinical findings into clinical investigations.
A combination of Deferoxamine mesylate and minimally invasive surgery with hematoma lysis for evacuation of intracerebral hemorrhage
Intracerebral hemorrhage is associated with significant morbidity and mortality. Some clinical trials demonstrated a trend towards benefit with surgical evacuation of intracerebral hemorrhage, without strong statistically significant results. Subsequent studies focused on minimally invasive techniques. Improved outcomes were more likely with surgical reduction of intracerebral hemorrhage volume to ≒15 mL. Deferoxamine is currently being evaluated as a therapeutic tool in intracerebral hemorrhage with promising results. There continues to be a lack of level I evidence supporting medical and surgical tools for intracerebral hemorrhage evacuation. Could a combination of minimally invasive surgery with hematoma lysis and Deferoxamine result in more effective hematoma evacuation?
Challenges and Opportunities of Deferoxamine Delivery for Treatment of Alzheimer's Disease, Parkinson's Disease, and Intracerebral Hemorrhage
Deferoxamine mesylate (DFO) is an FDA-approved, hexadentate iron chelator routinely used to alleviate systemic iron burden in thalassemia major and sickle cell patients. Iron accumulation in these disease states results from the repeated blood transfusions required to manage these conditions. Iron accumulation has also been implicated in the pathogenesis of Alzheimer's disease (AD), Parkinson's disease (PD), and secondary injury following intracerebral hemorrhage (ICH). Chelation of brain iron is thus a promising therapeutic strategy for improving behavioral outcomes and slowing neurodegeneration in the aforementioned disease states, though the effectiveness of DFO treatment is limited on several accounts. Systemically administered DFO results in nonspecific toxicity at high doses, and the drug's short half-life leads to low patient compliance. Mixed reports of DFO's ability to cross the blood-brain barrier (BBB) also appear in literature. These limitations necessitate novel DFO formulations prior to the drug's widespread use in managing neurodegeneration. Herein, we discuss the various dosing regimens and formulations employed in intranasal (IN) or systemic DFO treatment, as well as the physiological and behavioral outcomes observed in animal models of AD, PD, and ICH. The clinical progress of chelation therapy with DFO in managing neurodegeneration is also evaluated. Finally, the elimination of intranasally administered particles via the glymphatic system and efflux transporters is discussed. Abundant preclinical evidence suggests that intranasal DFO treatment improves memory retention and behavioral outcome in rodent models of AD, PD, and ICH. Several other biochemical and physiological metrics, such as tau phosphorylation, the survival of tyrosine hydroxylase-positive neurons, and infarct volume, are also positively affected by intranasal DFO treatment. However, dosing regimens are inconsistent across studies, and little is known about brain DFO concentration following treatment. Systemic DFO treatment yields similar results, and some complex formulations have been developed to improve permeability across the BBB. However, despite the success in preclinical models, clinical translation is limited with most clinical evidence investigating DFO treatment in ICH patients, where high-dose treatment has proven dangerous and dosing regimens are not consistent across studies. DFO is a strong drug candidate for managing neurodegeneration in the aging population, but before it can be routinely implemented as a therapeutic agent, dosing regimens must be standardized, and brain DFO content following drug administration must be understood and controlled via novel formulations.
Deferoxamine mesylate in patients with intracerebral haemorrhage (i-DEF): a multicentre, randomised, placebo-controlled, double-blind phase 2 trial
Background: Iron from haemolysed blood is implicated in secondary injury after intracerebral haemorrhage. We aimed to assess the safety of the iron chelator deferoxamine mesylate in patients with intracerebral haemorrhage and to establish whether the drug merits investigation in a phase 3 trial.
Methods: We did a multicentre, futility-design, randomised, placebo-controlled, double-blind, phase 2 trial at 40 hospitals in Canada and the USA. Adults aged 18-80 years with primary, spontaneous, supratentorial intracerebral haemorrhage were randomly assigned (1:1) to receive deferoxamine mesylate (32 mg/kg per day) or placebo (saline) infusions for 3 consecutive days within 24 h of haemorrhage onset. Randomisation was done via a web-based trial-management system centrally in real time, and treatment allocation was concealed from both participants and investigators. The primary outcome was good clinical outcome, which was defined as a modified Rankin Scale score of 0-2 at day 90. We did a futility analysis: if the 90% upper confidence bound of the absolute risk difference between the two groups in the proportion of participants with a good clinical outcome was less than 12% in favour of deferoxamine mesylate, then to move to a phase 3 efficacy trial would be futile. Primary outcome and safety data were analysed in the modified intention-to-treat population, comprising only participants in whom the study infusions were initiated. This trial is registered with ClinicalTrials.gov, number NCT02175225, and is completed.
Findings: We recruited 294 participants between Nov 23, 2014, and Nov 10, 2017. The modified intention-to-treat population consisted of 144 patients assigned to the deferoxamine mesylate group and 147 assigned to the placebo group. At day 90, among patients with available data for the primary outcome, 48 (34%) of 140 participants in the deferoxamine mesylate group, and 47 (33%) of 143 patients in the placebo group, had modified Rankin Scale scores of 0-2 (adjusted absolute risk difference 0﹞6% [90% upper confidence bound 6﹞8%]). By day 90, 70 serious adverse events were reported in 39 (27%) of 144 patients in the deferoxamine mesylate group, and 78 serious adverse events were reported in 49 (33%) of 147 patients in the placebo group. Ten (7%) participants in the deferoxamine mesylate and 11 (7%) in the placebo group died. None of the deaths were judged to be treatment related.
Interpretation: Deferoxamine mesylate was safe. However, the primary result showed that further study of the efficacy of deferoxamine mesylate with anticipation that the drug would significantly improve the chance of good clinical outcome (ie, mRS score of 0-2) at day 90 would be futile.
Funding: US National Institutes of Health and US National Institute of Neurological Disorders and Stroke.
PM2.5 induces ferroptosis in human endothelial cells through iron overload and redox imbalance
PM2.5 is becoming a worldwide environmental problem, which profoundly endangers public health, thus progressively capturing public attention this decade. As a fragile target of PM2.5, the underlying mechanisms of endothelial cell damage are still obscure. According to the previous microarray data and signaling pathway analysis, a new form of cell death termed ferroptosis in the current study is proposed following PM2.5 exposure. In order to verify the vital role of ferroptosis in PM2.5-induced endothelial lesion and further understand the potential mechanism involved, intracellular iron content, ROS release and lipid peroxidation, as well as biomarkers of ferroptosis were detected, respectively. As a result, uptake of particles increases cellular iron content and ROS production. Meanwhile, GSH depletion, and the decrease of GSH-Px and NADPH play significant roles in PM2.5-induced endothelial cell ferroptosis. Moreover, significantly changed expression of TFRC, FTL and FTH1 hinted that dysfunction of iron uptake and storage is a major inducer of ferroptosis. Importantly, index monitored above can be partially rescued by lipid peroxidation inhibitor ferrostatin-1 and iron chelator deferoxamine mesylate, which mediated antiferroptosis activity mainly depends on the restoration of antioxidant activity and iron metabolism. In conclusion, our data basically show that PM2.5 enhances ferroptosis sensitivity with increased ferroptotic events in endothelial cells, in which iron overload, lipid peroxidation and redox imbalance act pivotal roles.