Aminaftone (Aminaftone)
(Synonyms: Aminaftone; Aminaphthone) 目录号 : GC32548
Aminaftone (Aminaftone) 是 4-氨基苯甲酸的衍生物，通过干扰 pre-pro-ET-1 基因的转录，在体外下调 endothelin-1 (ET-1) 的产生。
Cas No.:14748-94-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | Human ECV304 endothelial cells are incubated with interleukin-1beta (IL-1beta) 100 IU/mL with or without the addition of increasing concentrations of Aminaftone (2, 4 or 6 μg/mL). ET-1 concentrations in surnatants are quantified by enzyme immunoassay kit at 3, 6 and 12 hours. PPET-1 gene expressions are also analysed by real-time polymerase chain reaction (RT-PCR) at the same time points. ECE activity is also determined[1]. |
Animal experiment: | Rats[2] Male Wistar rats weighing 300±30 g are randomly assigned to one of the following four experimental groups: 1) control healthy rats (n=11); 2) only injection of Monocrotaline (n=12); 3) injection of Monocrotaline followed by Aminaftone 30 mg/kg treatment (Aminaftone30) (n=8); and 4) injection of Monocrotaline followed by Aminaftone 150 mg/kg treatment (Aminaftone150) (n=8). Aminaftone is administered as food admix. Rats are weighed twice a week. |
References: [1]. Scorza R, et al. Aminaftone, a derivative of 4-aminobenzoic acid, downregulates endothelin-1 production in ECV304 Cells: an in vitro Study. Drugs R D. 2008;9(4):251-7. | |
Aminaftone, a derivative of 4-aminobenzoic acid, downregulates endothelin-1 (ET-1) production in vitro by interfering with the transcription of the pre-pro-ET-1 gene.
Aminaftone inhibits Endothelin-1 (ET-1) production in cell cultures by interfering with transcription of the pre-pro-endothelin-1 (PPET-1) gene. Incubation with IL-1beta increases concentrations of ET-1 and PPET-1 relative gene expression. Incubation with Aminaftone significantly reduces production of ET-1 in a concentration-dependent manner. A strong direct correlation is found between ET-1 concentrations and PPET-1 relative gene expression, but Aminaftone does not influence endothelin-converting enzyme (ECE) activity[1].
The rats are randomly assigned to the following experimental groups: Control; Monocrotaline; Aminaftone 30 mg/kg/day; Aminaftone 150 mg/kg/day. After 5 weeks, mortality is significantly lower in the animals treated with Aminaftone at both doses compared to Monocrotaline alone. Aminaftone reduces plasma concentration of ET-1 and seems to reduce right heart hypertrophy and the wall thickness of the pulmonary arteries at the highest dose. At the end of the experiment, no rats die in the control and Aminaftone 150 groups, while mortality is 38% in the Monocrotaline group and 13% in the Aminaftone 30 group. Overall, Aminaftone treated rats have a significantly lower mortality compared to rats in the Monocrotaline group (P=0.044)[2].
[1]. Scorza R, et al. Aminaftone, a derivative of 4-aminobenzoic acid, downregulates endothelin-1 production in ECV304 Cells: an in vitro Study. Drugs R D. 2008;9(4):251-7. [2]. Zambelli V, et al. Efficacy of aminaftone in a rat model of monocrotaline-induced pulmonary hypertension. Eur J Pharmacol. 2011 Sep 30;667(1-3):287-91.
| Cas No. | 14748-94-8 | SDF | |
| 别名 | Aminaftone; Aminaphthone | ||
| Canonical SMILES | OC1=C2C=CC=CC2=C(O)C(C)=C1OC(C3=CC=C(N)C=C3)=O | ||
| 分子式 | C18H15NO4 | 分子量 | 309.32 |
| 溶解度 | Soluble 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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1 mg | 5 mg | 10 mg |
| 1 mM | 3.2329 mL | 16.1645 mL | 32.329 mL |
| 5 mM | 0.6466 mL | 3.2329 mL | 6.4658 mL |
| 10 mM | 0.3233 mL | 1.6164 mL | 3.2329 mL |
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Phlebotonics for venous insufficiency
Cochrane Database Syst Rev 2020 Nov 3;11(11):CD003229.PMID:33141449DOI:10.1002/14651858.CD003229.pub4.
Background: Chronic venous insufficiency (CVI) is a condition in which veins are unable to transport blood unidirectionally towards the heart. CVI usually occurs in the lower limbs. It might result in considerable discomfort, with symptoms such as pain, itchiness and tiredness in the legs. Patients with CVI may also experience swelling and ulcers. Phlebotonics are a class of drugs often used to treat CVI. This is the second update of a review first published in 2005. Objectives: To assess the efficacy and safety of phlebotonics administered orally or topically for treatment of signs and symptoms of lower extremity CVI. Search methods: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and Clinicaltrials.gov trials register up to 12 November 2019. We searched the reference lists of the articles retrieved by electronic searches for additional citations. We also contacted authors of unpublished studies. Selection criteria: We included randomised, double-blind, placebo-controlled trials (RCTs) assessing the efficacy of phlebotonics (rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, Centella asiatica, disodium flavodate, French maritime pine bark extract, grape seed extract and Aminaftone) in patients with CVI at any stage of the disease. Data collection and analysis: Two review authors independently extracted data and assessed the quality of included RCTs. We estimated the effects of treatment by using risk ratios (RRs), mean differences (MDs) and standardized mean differences (SMDs), according to the outcome assessed. We calculated 95% confidence intervals (CIs) and percentage of heterogeneity (I2). Outcomes of interest were oedema, quality of life (QoL), assessment of CVI and adverse events. We used GRADE criteria to assess the certainty of the evidence. Main results: We identified three new studies for this update. In total, 69 RCTs of oral phlebotonics were included, but only 56 studies (7690 participants, mean age 50 years) provided quantifiable data for the efficacy analysis. These studies used different phlebotonics (28 on rutosides, 11 on hidrosmine and diosmine, 10 on calcium dobesilate, two on Centella asiatica, two on Aminaftone, two on French maritime pine bark extract and one on grape seed extract). No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria. Moderate-certainty evidence suggests that phlebotonics probably reduce oedema slightly in the lower legs, compared with placebo (RR 0.70, 95% CI 0.63 to 0.78; 13 studies; 1245 participants); and probably reduce ankle circumference (MD -4.27 mm, 95% CI -5.61 to -2.93 mm; 15 studies; 2010 participants). Moderate-certainty evidence shows that phlebotonics probably make little or no difference in QoL compared with placebo (SMD -0.06, 95% CI -0.22 to 0.10; five studies; 1639 participants); and similarly, may have little or no effect on ulcer healing (RR 0.94, 95% CI 0.79 to 1.13; six studies; 461 participants; low-certainty evidence). Thirty-seven studies reported on adverse events. Pooled data suggest that phlebotonics probably increase adverse events slightly, compared to placebo (RR 1.14, 95% CI 1.02 to 1.27; 37 studies; 5789 participants; moderate-certainty evidence). Gastrointestinal disorders were the most frequently reported adverse events. We downgraded our certainty in the evidence from 'high' to 'moderate' because of risk of bias concerns, and further to 'low' because of imprecision. Authors' conclusions: There is moderate-certainty evidence that phlebotonics probably reduce oedema slightly, compared to placebo; moderate-certainty evidence of little or no difference in QoL; and low-certainty evidence that these drugs do not influence ulcer healing. Moderate-certainty evidence suggests that phlebotonics are probably associated with a higher risk of adverse events than placebo. Studies included in this systematic review provided only short-term safety data; therefore, the medium- and long-term safety of phlebotonics could not be estimated. Findings for specific groups of phlebotonics are limited due to small study numbers and heterogeneous results. Additional high-quality RCTs focusing on clinically important outcomes are needed to improve the evidence base.
Phlebotonics for venous insufficiency
Cochrane Database Syst Rev 2016 Apr 6;4(4):CD003229.PMID:27048768DOI:10.1002/14651858.CD003229.pub3.
Background: Chronic venous insufficiency (CVI) is a common condition caused by valvular dysfunction with or without associated obstruction, usually in the lower limbs. It might result in considerable discomfort with symptoms such as pain, itchiness and tiredness in the legs. Patients with CVI may also experience swelling and ulcers. Phlebotonics are a class of drugs often used to treat CVI. This is an update of a review first published in 2005. Objectives: To assess the efficacy and safety of phlebotonics administered both orally and topically for treatment of signs and symptoms of lower extremity CVI. Search methods: For this update, the Cochrane Vascular Trials Search Co-ordinator (TSC) searched the Specialised Register (August 2015), as well as the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 7). The reference lists of the articles retrieved by electronic searches were searched for additional citations. We also contacted pharmaceutical companies and searched the World Health Organization (WHO) International Clinical Trials Registry Platform Search Portal for ongoing studies (last searched in August 2015). Selection criteria: Randomised, double-blind, placebo-controlled trials (RCTs) assessing the efficacy of rutosides, hidrosmine, diosmine, calcium dobesilate, chromocarbe, Centella asiatica, disodium flavodate, french maritime pine bark extract, grape seed extract and Aminaftone in patients with CVI at any stage of the disease. Data collection and analysis: Two review authors independently extracted data and assessed the quality of included RCTs. We estimated the effects of treatment by using risk ratios (RRs), mean differences (MDs) and standardised mean differences (SMDs), according to the outcome assessed. We calculated 95% confidence interval (CIs) and percentage of heterogeneity (I(2)). Additionally, we performed sensitivity analyses. Main results: We included 66 RCTs of oral phlebotonics, but only 53 trials provided quantifiable data (involving 6013 participants; mean age 50 years) for the efficacy analysis: 28 for rutosides, 10 hidrosmine and diosmine, nine calcium dobesilate, two Centella asiatica, two Aminaftone, two french maritime pine bark extract and one grape seed extract. No studies evaluating topical phlebotonics, chromocarbe, naftazone or disodium flavodate fulfilled the inclusion criteria.Moderate-quality evidence suggests that phlebotonics reduced oedema in the lower legs compared with placebo. Phlebotonics showed beneficial effects among participants including reduced oedema (RR 0.70, 95% CI 0.63 to 0.78; I(2) = 20%; 1245 participants) and ankle circumference (MD -4.27 mm, 95% CI -5.61 to -2.93 mm; I(2) = 47%; 2010 participants). Low-quality evidence reveals no difference in the proportion of ulcers cured with phlebotonics compared with placebo (RR 0.94, 95% CI 0.79 to 1.13; I(2) = 5%; 461 participants). In addition, phlebotonics showed greater efficacy for trophic disorders, cramps, restless legs, swelling and paraesthesia, when compared with placebo. We identified heterogeneity for the variables of pain, itching, heaviness, quality of life and global assessment by participants. For quality of life, it was not possible to pool the studies because heterogeneity was high. However, high-quality evidence suggests no differences in quality of life for calcium dobesilate compared with placebo (MD -0.60, 95% CI -2.15 to 0.95; I(2) = 40%; 617 participants), and low-quality evidence indicates that in the Aminaftone group, quality of life was improved over that reported in the placebo group (MD -10.00, 95% CI -17.01 to - 2.99; 79 participants). Moderate-quality evidence shows that the phlebotonics group had greater risk of non-severe adverse events than the placebo group (RR 1.21, 95% CI 1.05 to 1.41; I(2) = 0; 3975 participants). Gastrointestinal disorders were the most frequently reported adverse events. Authors' conclusions: Moderate-quality evidence shows that phlebotonics may have beneficial effects on oedema and on some signs and symptoms related to CVI such as trophic disorders, cramps, restless legs, swelling and paraesthesia when compared with placebo but can produce more adverse effects. Phlebotonics showed no differences compared with placebo in ulcer healing. Additional high-quality RCTs focused on clinically important outcomes are needed to improve the evidence base.
Aminaftone, a derivative of 4-aminobenzoic acid, downregulates endothelin-1 production in ECV304 Cells: an in vitro Study
Drugs R D 2008;9(4):251-7.PMID:18588356DOI:10.2165/00126839-200809040-00005.
Background and objective: Endothelin-1 (ET-1) plays a central role in the pathogenesis of several vascular diseases. Aminaftone is a drug used for the treatment of capillary disorders but which has a mechanism of action that is not fully understood. We investigated whether Aminaftone may exert its effect by interfering with the production of ET-1. Methods: Human ECV304 endothelial cells were incubated with interleukin-1beta (IL-1beta) 100 IU/mL with or without the addition of increasing concentrations of Aminaftone (2, 4 or 6 microg/mL). ET-1 concentrations in surnatants were quantified by enzyme immunoassay kit at 3, 6 and 12 hours. Pre-pro-endothelin-1 (PPET-1) gene expressions were also analysed by real-time polymerase chain reaction (RT-PCR) at the same time points. Endothelin-converting enzyme (ECE) activity was also determined. Results: Incubation with IL-1beta increased concentrations of ET-1 and PPET-1 relative gene expression. Incubation with Aminaftone significantly reduced production of ET-1 in a concentration-dependent manner. A strong direct correlation was found between ET-1 concentrations and PPET-1 relative gene expression, but Aminaftone did not influence ECE activity. Conclusion: Aminaftone inhibits ET-1 production in cell cultures by interfering with transcription of the PPET-1 gene. These findings may account for the clinical efficacy of Aminaftone in the treatment of capillary disorders and may encourage conduct of further clinical trials.
Efficacy of Aminaftone in a rat model of monocrotaline-induced pulmonary hypertension
Eur J Pharmacol 2011 Sep 30;667(1-3):287-91.PMID:21641342DOI:10.1016/j.ejphar.2011.05.060.
Pulmonary hypertension is characterized by increased vascular resistances, that could lead to right heart failure and death. Endothelin-1 (ET-1) is a peptide with strong vasoconstrictive and pro-fibrotic properties and is one of the main mediators of pulmonary hypertension. Aminaftone, a synthetic molecule derivative of 4-amynobenzoic acid, down-regulates ET-1 production in vitro by interfering with the transcription of the pre-pro-ET-1 gene. The aim of this study was to test whether the inhibition of ET-1 production by Aminaftone attenuates the effects of pulmonary hypertension. Pulmonary hypertension was induced through s.c. injection of 60 mg/kg monocrotaline. The rats were randomly assigned to the following experimental groups: Control; Monocrotaline; Aminaftone 30 mg/kg/day; Aminaftone 150 mg/kg/day. After 5 weeks, mortality was significantly lower in the animals treated with Aminaftone at both doses compared to monocrotaline alone. Aminaftone reduced plasma concentration of ET-1 and seemed to reduce right heart hypertrophy and the wall thickness of the pulmonary arteries at the highest dose. Aminaftone may represent a novel treatment strategy of pulmonary hypertension.
3-Methyl-1,4-dioxo-1,4-dihydro-naphthalen-2-yl 4-amino-benzoate
Acta Crystallogr Sect E Struct Rep Online 2008 Mar 14;64(Pt 4):o718.PMID:21202108DOI:10.1107/S1600536808005308.
The crystal structure of the title compound, C(18)H(13)NO(4), the oxidized form of the drug Aminaftone used in venous disease therapy, is characterized by the presence of ribbons of hydrogen-bonded mol-ecules parallel to the [111] crystallographic direction and by stacking inter-actions between rings [centroid-centroid distance between quinone rings = 3.684 (3) Å and between amino-benzoate rings = 4.157 (3) Å] along the ribbons.