Doxorubicin
(Synonyms: 阿霉素; Hydroxydaunorubicin) 目录号 : GC16994
多柔比星（Doxorubicin，简称DOX），也被称为阿霉素，是一种蒽环类化合物，具有最广泛的活性谱。
Cas No.:23214-92-8
Sample solution is provided at 25 µL, 10mM.
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Related Biological Data
Knockdown of RPS27a regulates p53 activity without afecting its stability in response to stress.D NC and RPS27a knockdown A549 cells were treated with 30nM Dox for 6, 12 or 24h, and the protein expression was detected with IB.
Briefy, the cells grew to 70% confuence, 30nM Dox(GlpBio) was added and incubated 24h, and the cells were then digested with 0.25% trypsin.
J Exp Clin Canc Res, 2022, 41(1): 1-20. PMID: 35073964 IF: 11.164 -
Related Biological Data
QSG provided protection against cardiac damage brought on by DOX.
QSG (2.5 g/kg and 5 g/kg) and pravastatin (40 mg/kg) gavage was used to administer the solution in ultrapure water for five days before intravenous injection of DOX(GlpBio) at day 6. Mice in the treatment group continued to receive gavage treatment until day 11. On day 6 and 9 of the trial, mice in the model and treatment groups received 6 mg/kg of DOX intravenously.
Journal of Ethnopharmacology, 2023: 117134. PMID: 37714227 IF: 5.3999 -
Related Biological Data
miR-188-5 binds to the PTEN 3'UTR. (D) The binding relationship between miR-188-5p and PTEN in THP-1/ADM and Kasumi-1/ADM cells by dual-luciferase reporter assays.
ADM-resistant AML cells were established by exposure to incremental doses of ADM (GC16994, Glpbio). In brief, THP-1 and Kasumi-1 cells were seeded into complete culture medium containing 2 nM ADM and incubated for 48 h. Subsequently, the medium was replaced with fresh medium (without ADM) and cultured until cell viability was ≥ 90%.
Arch Biochem Biophys (2023): 109523. PMID: 36682704 IF: 4.1137
Quality Control & SDS
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| Cell experiment [1]: | |
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Cell lines |
Human lung carcinoma (A549) cell lines |
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Preparation Method |
About 1×105 A549 cells/well were plated into 12-well culture dishes and incubated for 24h. After 24h, doxorubicin, as well as conjugates of doxorubicin at a concentration equivalent to 2µg/ml of doxorubicin was added and incubated for time periods of 4 and 12h. |
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Reaction Conditions |
2µg/ml |
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Applications |
The uptake of the free doxorubicin and conjugates into the A549 cells increased with time. The fluorescent images of cells treated with free doxorubicin and polymannose(PM)-doxorubicin showed better uptake, while the sodium alginate(SA)-doxorubicin showed significantly lesser uptake after 4 and 12h exposure. |
| Animal experiment [2]: | |
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Animal models |
BALB/c mice (5-6 weeks, female) and BALB/c athymic nude mice (nu/nu, 5-6 weeks, male) |
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Preparation Method |
For in vivo tumor implantation, C26 cells at 5×105 cells in 30µL Minimum Essential Medium (MEM) and MIA PaCa-2 cells at 2×106cells in 50µL 10:90 v/v MEM: Matrigel matrix were inoculated in the right flank of normal and athymic nude BALB/c mice, respectively. Tumor cells were allowed to grow until the tumor volume-reached 75-100mm3 for C26 tumors and 100-125mm3 for MIA PaCa-2 tumors. Tumor-bearing mice were then treated with a single i.v. injection of albumin-binding domain-doxorubicin (ABD-DoX) at 10 and 20mg doxorubicin equiv. kg-1 BW, AlDoxorubicin at 20mg doxorubicin equiv. kg-1 BW, and free doxorubicin at 10mg·kg-1 BW. |
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Dosage form |
ABD-Doxorubicin at 10 and 20mg doxorubicin equiv. kg-1 BW, AlDoxorubicin at 20mg doxorubicin equiv. kg-1 BW, and free doxorubicin at 10mg kg-1 BW. |
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Applications |
ABD-Doxorubicin has superior therapeutic efficacy to AlDoxorubicin in the syngeneic C26 colon carcinoma model in BALB/c mice and in the MIA PaCa-2 pancreatic adenocarcinoma xenograft model in nude mice, and that both formulations are superior to free Doxorubicin. |
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References: [1]. Francis AP, Jayakrishnan A. Conjugating doxorubicin to polymannose: a new strategy for target specific delivery to lung cancer cells. J Biomater Sci Polym Ed. 2019;30(16):1471-1488. [2]. Yousefpour P, Ahn L, et al. Conjugate of Doxorubicin to Albumin-Binding Peptide Outperforms Aldoxorubicin. Small. 2019;15(12):e1804452. |
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Doxorubicin(DOX), also known as adriamycin, is a compound of the anthracycline class that has the broadest spectrum of activity[1]. Doxorubicin inhibits topoisomerase Ⅱ and topoisomerase Ⅰ with IC50 of 2.67μM and 0.8μM, respectively[2,3]. It is widely used for the treatment of various solid tumors via interacting with deoxyribonucleic acid, but it is limited in the clinical application due to severe side effect[4]
Doxorubicin can be loaded into liposomes by transmembrane pH gradient method to get high encapsulation efficiency with high drug/lipid ratio. Liposomal doxorubicin is a successful clinical formulation, and also a perfect model drug system for cancer-therapy research[5]. A considerable amount of doxorubicin can accumulate in human placental tissue. Both doxorubicin and its pH-sensitive liposomal formulation, L-Doxorubicin, are efficiently internalized by human trophoblastic BeWo cells and that doxorubicin accumulates in placental tissue so that decrease the exposure of fetal[6]
Doxorubicin combines with cobimetinib at sublethal dose completely arrested osteosarcoma growth. Targeted MEK inhibition by cobimetinib enhances doxorubicin’s efficacy in osteosarcoma models[7]. Doxorubicin is frequently used as an adjuvant chemotherapeutic agent for breast cancer. Silk films loaded with doxorubicin provide locoregional control of human breast cancer in vivo. By manipulating silk crystallinity or β-sheet content, the doxorubicin release rate could be controlled. Both soluble and stabilised silk films loaded with doxorubicin had a significantly greater primary tumour response than the equivalent dose of doxorubicin administered intravenously in the absence of the silk film carrier. The future use of this approach for localised chemotherapy is promising[8]
References:
[1].Escoffre JM, Piron J, et al. Doxorubicin delivery into tumor cells with ultrasound and microbubbles. Mol Pharm. 2011;8(3):799-806.
[2].Rhee HK, Park HJ, et al. Synthesis, cytotoxicity, and DNA topoisomerase II inhibitory activity of benzofuroquinolinediones. Bioorg Med Chem. 2007 Feb 15;15(4):1651-8.
[3].Foglesong PD, Reckord C, Swink S. Doxorubicin inhibits human DNA topoisomerase I. Cancer Chemother Pharmacol. 1992;30(2):123-5.
[4].Jie L, Lang D, et al. Superparamagnetic Iron Oxide Nanoparticles/Doxorubicin-Loaded Starch-Octanoic Micelles for Targeted Tumor Therapy. J Nanosci Nanotechnol. 2019;19(9):5456-5462.
[5].Soininen SK, Repo JK, et al. Human placental cell and tissue uptake of doxorubicin and its liposomal formulations. Toxicol Lett. 2015;239(2):108-114.
[6].Niu G, Cogburn B, et al. Preparation and characterization of doxorubicin liposomes. Methods Mol Biol. 2010;624:211-219.
[7].Seib FP, Kaplan DL. Doxorubicin-loaded silk films: drug-silk interactions and in vivo performance in human orthotopic breast cancer. Biomaterials. 2012;33(33):8442-8450.
[8]. Ma L, Xu Y, Xu X. Targeted MEK inhibition by cobimetinib enhances doxorubicin's efficacy in osteosarcoma models. Biochem Biophys Res Commun. 2020;529(3):622-628.
多柔比星（Doxorubicin,简称DOX）,也被称为阿霉素,是一种蒽环类化合物,具有最广泛的活性谱[1]。DOX通过抑制拓扑异构酶Ⅱ和拓扑异构酶Ⅰ来发挥作用,其IC50分别为2.67μM和0.8μM[2,3]。它广泛用于治疗各种实体肿瘤,并与脱氧核糖核酸相互作用,但由于严重的副作用,在临床应用中受到限制[4]。
多柔比星可以通过跨膜pH梯度法装载到脂质体中,以高药物/脂质比获取高的封装效率。脂质体多柔比星是一种成功的临床制剂,也是癌症治疗研究的完美模型药物系统[5]。相当数量的多柔比星可以在人类胎盘组织中积累。多柔比星及其pH敏感性脂质体配方L-Doxorubicin都能够有效地内化到人类滋养层BeWo细胞中,并且多柔比星会在胎盘组织中积累,从而降低了胎儿暴露[6]。
多柔比星与可比替尼在亚致死剂量下结合,完全阻止了骨肉瘤的生长。通过可比替尼靶向抑制MEK增强了多柔比星在骨肉瘤模型中的功效。多柔比星常被用作乳腺癌辅助化疗药物。装载有多柔比星的丝素膜能够提供体内人类乳腺癌局部控制。通过调节丝素晶态或β-折叠含量,可以控制多柔比星释放速率。与不带丝素载体的等效剂量静脉注射相比,既溶解性又稳定的装载有多柔比星的丝素膜具有显着更大的原发肿瘤反应。这种方法未来在局部化学治疗方面具有很大潜力。
| Cas No. | 23214-92-8 | SDF | |
| 别名 | 阿霉素; Hydroxydaunorubicin | ||
| 化学名 | (7S,9S)-7-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione | ||
| Canonical SMILES | CC1C(C(CC(O1)OC2CC(CC3=C(C4=C(C(=C23)O)C(=O)C5=C(C4=O)C=CC=C5OC)O)(C(=O)CO)O)N)O | ||
| 分子式 | C27H29NO11 | 分子量 | 543.52 |
| 溶解度 | 20mg/mL in Water(Need ultrasonic); 20mg/mL in DMSO(Need ultrasonic) | 储存条件 | Store at -20°C, protect from light |
| 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 | 1.8399 mL | 9.1993 mL | 18.3986 mL |
| 5 mM | 0.368 mL | 1.8399 mL | 3.6797 mL |
| 10 mM | 0.184 mL | 0.9199 mL | 1.8399 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
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。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
An overview of doxorubicin formulations in cancer therapy
The burden of cancer is continuously increasing, and is rapidly becoming a global pandemic. The first liposomal encapsulated anticancer drug which received clinical approval against malignancies including solid tumours, transplantable leukemias and lymphomas was Doxorubicin HCl. This review is aimed at providing an overview of doxorubicin in cancer therapy. Pegylated liposomal doxorubicin has a polyethylene glycol (PEG) layer around doxorubicin-containing liposome as the result of a process known as pegylation. Non-pegylated liposomal doxorubicin (NPLD) was developed to overcome the drawbacks associated with previous formulations. Nudoxa; (NPLD) with its unique drug delivery system offers the benefit of pegylated liposomal doxorubicin without hand foot syndrome as the major side effect. Future studies will be directed towards estimating the costs of treatment with the novel liposomal doxorubicin formulations in order to assess their widespread use and robustness in treating patients with cancer.
Doxorubicin: the good, the bad and the ugly effect
The anthracycline doxorubicin (DOX) is widely used in chemotherapy due to its efficacy in fighting a wide range of cancers such as carcinomas, sarcomas and hematological cancers. Despite extensive clinical utilization, the mechanisms of action of DOX remain under intense debate. A growing body of evidence supports the view that this drug can be a double-edge sword. Indeed, injury to nontargeted tissues often complicates cancer treatment by limiting therapeutic dosages of DOX and diminishing the quality of patients' life during and after DOX treatment. The literature shows that the heart is a preferential target of DOX toxicity. However, this anticancer drug also affects other organs like the brain, kidney and liver. This review is mainly devoted to discuss the mechanisms underlying not only DOX beneficial effects but also its toxic outcomes. Additionally, clinical studies focusing the therapeutic efficacy and side effects of DOX treatment will be discussed. Finally, some potential strategies to attenuate DOX-induced toxicity will be debated.
Clinical pharmacokinetics of doxorubicin
Doxorubicin (adriamycin) has a very wide antitumour spectrum, compared with other anticancer drugs; however, except for Hodgkin's disease, it is not associated with curative chemotherapy. Doxorubicin has been in clinical use for more than 2 decades, and only recently has it been recognised that the cytotoxic effect is produced at the cellular level by multiple mechanisms which have not yet been conclusively identified. Key factors are a combination of doxorubicin-induced free radical formation due to metabolic activation, deleterious actions at the level of the membrane, and drug-intercalation into DNA. Multiple aspects of the clinical pharmacokinetics of this drug have been described. Wide interpatient variations in plasma pharmacokinetics have been noted, but without firm relation to clinical outcome. An apparent volume of distribution of approximately 25 L/kg points to extensive uptake by tissues. Up to several weeks after administration, significant concentrations of doxorubicin have been found in haematopoietic cells and in several other tissues. The maximum cellular doxorubicin concentrations reached in vivo remain significantly below those at which all clonogenic leukaemic cells are killed in vitro. Doxorubicin has been administered as frequent (weekly) low doses, single high doses, and as a continuous infusion. The optimal schedule with respect to tumour cytotoxicity and dose-limiting side effects such as myelosuppression or cardiotoxicity, has never been investigated in a prospective, randomised manner. Clinical trials large enough to study optimal, and possibly individualised, doxorubicin chemotherapy need to be performed. This review summarises pharmacological and pharmacodynamic data of doxorubicin, and discusses these in relation to possible improvement of its therapeutic index. Furthermore, drug interactions, dose-response relationships, mechanisms of action, multidrug resistance, and treatment scheduling are discussed in the perspective of the development of novel treatment strategies.
The Synthesis of Nano-Doxorubicin and its Anticancer Effect
Doxorubicin (DOX) is widely used as a clinical first-line anti-cancer drug. However, its clinical application is severely limited due to the lack of tumor specificity of the drug and severe side effects such as myelosuppression, nephrotoxicity, dose-dependent cardiotoxicity, and multi-drug resistance. To improve the bioavailability of DOX, maximize the therapeutic effect, and reduce its toxicity and side effects, many studies have been done on the nanoformulations of DOX, such as liposomes, polymer micelles, dendrimer, and nanogels. Herein, we review the latest progress of DOX nano-preparations and their anti-tumor effects, hoping to provide theoretical references and new research ideas for the development of new dosage forms of the drug and the technical methods available for clinical application.
Doxorubicin-Based Hybrid Compounds as Potential Anticancer Agents: A Review
The scarcity of novel and effective therapeutics for the treatment of cancer is a pressing and alarming issue that needs to be prioritized. The number of cancer cases and deaths are increasing at a rapid rate worldwide. Doxorubicin, an anticancer agent, is currently used to treat several types of cancer. It disrupts myriad processes such as histone eviction, ceramide overproduction, DNA-adduct formation, reactive oxygen species generation, Ca2+, and iron hemostasis regulation. However, its use is limited by factors such as drug resistance, toxicity, and congestive heart failure reported in some patients. The combination of doxorubicin with other chemotherapeutic agents has been reported as an effective treatment option for cancer with few side effects. Thus, the hybridization of doxorubicin and other chemotherapeutic drugs is regarded as a promising approach that can lead to effective anticancer agents. This review gives an update on hybrid compounds containing the scaffolds of doxorubicin and its derivatives with potent chemotherapeutic effects.