Benzarone
(Synonyms: 苯扎隆,Fragivix) 目录号 : GC49403
An active metabolite of benzbromarone
Cas No.:1477-19-6
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Benzarone is an active metabolite of the urate anion transporter 1 (URAT1) inhibitor benzbromarone .1,2 It inhibits URAT1 in Xenopus oocytes expressing the human enzyme (IC50 = 2.8 µM).2 Benzarone also inhibits the tyrosine phosphatase activity of eyes absent homolog 3 (EYA3; IC50 = 17.5 µM), as well as reduces the proliferation and migration of human umbilical vein endothelial cells (HUVECs) when used at a concentration of 7.5 µM.3 It uncouples oxidative phosphorylation in isolated rat liver mitochondria and induces apoptosis and necrosis in isolated rat hepatocytes.4 Benzarone (25 µg/g) reduces tumor growth in an A-673 Ewing sarcoma mouse xenograft model.5
1.StÜber, W., and MÖller, H.Determination of benzbromarone, bromobenzarone and benzarone in plasma by gas chromatography—mass spectrometryJ. Chromatogr. B Biomed. Sci. Appl.224(2)327-331(1981) 2.Wempe, M.F., Jutabha, P., Quade, B., et al.Developing potent human uric acid transporter 1 (hURAT1) inhibitorsJ. Med. Chem.54(8)2701-2713(2011) 3.Pandey, R.N., Wang, T.S., Tadjuidje, E., et al.Structure-activity relationships of benzbromarone metabolites and derivatives as EYA inhibitory anti-angiogenic agentsPLoS One8(12)e84582(2013) 4.Kaufmann, P., TÖrÖk, M., HÄnni, A., et al.Mechanisms of benzarone and benzbromarone-induced hepatic toxicityHepatology41(4)925-935(2005) 5.Wang, Y., Pandey, R.N., Roychoudhury, K., et al.Targeting EYA3 in ewing sarcoma retards tumor growth and angiogenesisMol. Cancer Ther.20(5)803-815(2021)
| Cas No. | 1477-19-6 | SDF | |
| 别名 | 苯扎隆,Fragivix | ||
| Canonical SMILES | O=C(C1=C(CC)OC2=CC=CC=C12)C3=CC=C(C=C3)O | ||
| 分子式 | C17H14O3 | 分子量 | 266.3 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 10 mg/ml,Ethanol: 10 mg/ml | 储存条件 | -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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 3.7552 mL | 18.7758 mL | 37.5516 mL |
| 5 mM | 0.751 mL | 3.7552 mL | 7.5103 mL |
| 10 mM | 0.3755 mL | 1.8776 mL | 3.7552 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。
A Literature Review of Pharmacological Agents to Improve Venous Leg Ulcer Healing
Wounds 2020 Jul;32(7):195-207.PMID:33166265doi
Compression therapy is the gold standard treatment for venous leg ulcers (VLUs); however, with adjunctive pharmacological therapies and poor patient adherence using compressive dressings, clinicians are looking to find the advantage in treating VLUs. This literature review focuses on the efficacy of pharmacological agents, quality of life using agents in addition to compression therapy, and cost effectiveness to indicate the best outcomes for pharmacological treatment of VLUs. The following available venotonic, hemorheologic, and fibrinolytic agents were reviewed for oral management in treating VLUs: pentoxifylline, flavonoids (diosmin, hidrosmin, rutosides, and micronized purified flavonoid fraction, Vasculera), Red-Vine-Leaf-Extract AS 195, Ruscus, Ginkgo biloba, Centella asiatica, Pycnogenol (French maritime pine bark), escin/horse chestnut extract, nutritional supplements (ie, zinc and magnesium, glycosaminoglycans [sulodexide], mesoglycans), Axaven, cilostazol, fibrinolytic enhancers (stanozolol and defibrotide), calcium dobesilate, aspirin, antibiotics (antimicrobials, doxycycline, levamisole), diuretics, cinnarizine, naftazone, and Benzarone. Venous leg ulcer pharmacological treatment options were searched in the English language from February 2020 to March 2020 using numerous databases and sites, such as PubMed. Drugs used adjunctively with compression therapy that facilitate healing in long-standing or large VLUs include micronized purified flavonoid fraction, pentoxifylline, sulodexide, and mesoglycan.
Mechanisms of Benzarone and benzbromarone-induced hepatic toxicity
Hepatology 2005 Apr;41(4):925-35.PMID:15799034DOI:10.1002/hep.20634.
Treatment with Benzarone or benzbromarone can be associated with hepatic injury. Both drugs share structural similarities with amiodarone, a well-known mitochondrial toxin. Therefore, we investigated the hepatotoxicity of Benzarone and benzbromarone as well as the analogues benzofuran and 2-butylbenzofuran. In isolated rat hepatocytes, amiodarone, Benzarone, and benzbromarone (20 micromol/L) decreased mitochondrial membrane potential by 23%, 54% or 81%, respectively. Benzofuran and 2-butylbenzofuran had no effect up to 100 micromol/L. In isolated rat liver mitochondria, amiodarone, Benzarone, and benzbromarone, but not benzofuran, decreased state 3 oxidation and respiratory control ratios for L-glutamate (50% decrease of respiratory control ratio at [micromol/L]: amiodarone, 12.9; Benzarone, 10.8; benzbromarone, <1). Amiodarone, Benzarone, and benzbromarone, but not benzofuran, also uncoupled oxidative phosphorylation. Mitochondrial beta-oxidation was decreased by 71%, 87%, and 58% with 100 micromol/L amiodarone or Benzarone and 50 micromol/L benzbromarone, respectively, but was unaffected by benzofuran, whereas ketogenesis was not affected. 2-Butylbenzofuran weakly inhibited state 3 oxidation and beta-oxidation only at 100 micromol/L. In the presence of 100 micromol/L amiodarone, Benzarone or benzbromarone, reactive oxygen species production was increased, mitochondrial leakage of cytochrome c was induced in HepG2 cells, and permeability transition was induced in isolated rat liver mitochondria. At the same concentrations, amiodarone, Benzarone, and benzbromarone induced apoptosis and necrosis of isolated rat hepatocytes. In conclusion, hepatotoxicity associated with amiodarone, Benzarone, and benzbromarone can at least in part be explained by their mitochondrial toxicity and the subsequent induction of apoptosis and necrosis. Side chains attached to the furan moiety are necessary for rendering benzofuran hepatotoxic.
Metabolic fate of the thrombolytic agent Benzarone in man: comparison with the rat and dog
Xenobiotica 1987 Jul;17(7):881-96.PMID:3660858DOI:10.3109/00498258709043998.
1. The metabolic fate of 14C-benzarone in the rat and dog has been compared to that in human subjects. An oral dose was well-absorbed in all three species. However, the 14C excretion patterns differed: humans (100 mg) excreted means of 73 and 19% dose in the urine and faeces respectively, whereas the rat (2 mg/kg) and dog (0.5 mg/kg) excreted greater than 80% in the faeces, mostly during the first 48 h. 2. Much of the faecal 14C was attributable to 14C excreted in the bile which amounted to 59% in the 7 h bile collected from an intravenously dosed dog, and a mean of 72% in the 24 h bile of orally dosed rats. Enterohepatic circulation of 14C was demonstrated in rats. 3. Total 14C in human plasma reached peak concentrations between 1-2 h and declined relatively rapidly, to about 10% of this value within 24 h. Unchanged Benzarone was not detected in plasma (less than 25 ng/ml), even after a 400 mg dose, but conjugated Benzarone was--accounting for about 10% of the peak concentration of 14C. In the dog, by contrast, conjugated Benzarone accounted for about 50% of the peak concentration of 14C of 0.96 microgram equiv./ml at 1 h. The extent of binding of Benzarone to human plasma proteins (greater than 99%; in vitro was slightly greater than that (greater than 96%) of total 14C (ex vivo, representing metabolites). 4. Examination of metabolite profiles by h.p.l.c. suggested that in the rat and dog, at least 70% absorbed dose was eliminated by direct conjugation, whereas in humans at least 70% was hydroxylated before conjugation, mainly with glucuronic acid. Hydroxylation occurred in the benzofuran ring and/or the ethyl side-chain. The principal urinary metabolite in humans was the conjugate(s) of the 1-hydroxylated ethyl side-chain derivative (mean 26% dose).
Severe hepatotoxicity related to Benzarone: a report of three cases with two fatalities
Liver 1995 Feb;15(1):25-9.PMID:7776854DOI:10.1111/j.1600-0676.1995.tb00102.x.
We report three cases of severe hepatotoxicity related to Benzarone, a benzofuran derivative. Our cases include a 35-year-old woman with (sub)fulminant hepatitis, a 67-year-old woman with macronodular cirrhosis, and a 68-year-old man with severe chronic active hepatitis and cirrhosis, with positivity of anti-smooth muscle antibodies. Two patients died. We stress the potential of Benzarone to cause hepatotoxicity, which usually resembles severe chronic active hepatitis. Our cases constitute the most severe cases of Benzarone hepatotoxicity reported so far, and comprise the first cases of (sub)fulminant hepatitis and cirrhosis related to Benzarone.
Chronic active hepatitis caused by Benzarone
J Hepatol 1987 Dec;5(3):332-5.PMID:3429840DOI:10.1016/s0168-8278(87)80039-9.
We report a case of chronic active hepatitis caused by Benzarone, a benzofuran derivative used in Europe for the treatment of peripheral venous disorders. Jaundice and serum alanine aminotransferase activity increased while drug administration was continued, but promptly decreased when it was eventually interrupted. Liver lesions were those of chronic active hepatitis. Anti-smooth muscle antibodies were present at a titer of 1:500 and disappeared 8 months after withdrawal of Benzarone.