Desbutyl Lumefantrine
(Synonyms: Desbutyl-benflumetol) 目录号 : GC60757
An active metabolite of lumefantrine
Cas No.:355841-11-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
desbutyl Lumefantrine is an active metabolite of the antimalarial agent lumefantrine .1,2 It is formed from lumefantrine by the cytochrome P450 (CYP) isoform CYP3A4.3 desbutyl Lumefantrine is active against chloroquine-sensitive and -resistant strains of P. falciparum (IC50s = 9 and 9.5 nM, respectively).1 It inhibits the human-ether-a-go-go (hERG) potassium channel, also known as Kv11.1, in HEK293 cells expressing the human channel (IC50 = 5.49 ?M).2
1.Wong, R.P.M., Salman, S., Ilett, K.F., et al.Desbutyl-lumefantrine is a metabolite of lumefantrine with potent in vitro antimalarial activity that may influence artemether-lumefantrine treatment outcomeAntimicrob. Agents Chemother.55(3)1194-1198(2011) 2.Traebert, M., Dumotier, B., Meister, L., et al.Inhibition of hERG K+ currents by antimalarial drugs in stably transfected HEK293 cellsEur. J. Pharmacol.484(1)41-48(2004) 3.Abdullahi, S.T., Soyinka, J.O., Olagunju, A., et al.CYP2B6*6 genotype specific differences in artemether-lumefantrine disposition in healthy volunteersJ. Clin. Pharmacol.60(3)351-360(2020)
| Cas No. | 355841-11-1 | SDF | |
| 别名 | Desbutyl-benflumetol | ||
| Canonical SMILES | OC(CNCCCC)C1=CC(Cl)=CC(/C2=C\C3=CC=C(Cl)C=C3)=C1C4=C2C=C(Cl)C=C4 | ||
| 分子式 | C26H24Cl3NO | 分子量 | 472.83 |
| 溶解度 | 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 | 2.1149 mL | 10.5746 mL | 21.1493 mL |
| 5 mM | 0.423 mL | 2.1149 mL | 4.2299 mL |
| 10 mM | 0.2115 mL | 1.0575 mL | 2.1149 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。
Method development and validation for simultaneous determination of lumefantrine and its major metabolite, Desbutyl Lumefantrine in human plasma using RP-HPLC/UV detection
J Chromatogr B Analyt Technol Biomed Life Sci 2014 Jan 1;944:114-22.PMID:24316521DOI:10.1016/j.jchromb.2013.10.037.
A simple, specific, precise and rapid RP-HPLC-UV method was developed for simultaneous determination of lumefantrine and its metabolite Desbutyl Lumefantrine in human plasma. Experimental parameters were optimized and the method was validated according to standard guidelines. The method showed adequate separation for lumefantrine and Desbutyl Lumefantrine and best resolution was achieved with Supelco Discovery HS C18 RP (150mm×4.6mm, 5μm) column using acetonitrile and 0.05% trifluroacetic acid (70:30, v/v) as a mobile phase pumped at a flow rate of 1.0ml/min and wavelength of 335nm. The method was linear over the concentration range of 10-12,000ng/ml. The lower limit of detection (LLOD) and lower limit of quantification (LLOQ) for lumefantrine were 10.0 and 18.0ng/ml, while for Desbutyl Lumefantrine were 7.5 and 15.0ng/ml, respectively. The proposed method was efficiently applied for determination of lumefantrine and Desbutyl Lumefantrine concentrations in plasma samples for pharmacokinetic studies.
Influence of selected polymorphisms in disposition genes on lumefantrine pharmacokinetics when coadministered with efavirenz
Pharmacogenet Genomics 2020 Jul;30(5):96-106.PMID:32209837DOI:10.1097/FPC.0000000000000401.
Background: Coadministration of artemether-lumefantrine and efavirenz has been shown to result in significant interactions. The influence of functional genetic polymorphisms in selected CYPs on the magnitude of this interaction was investigated in pregnant and nonpregnant adults. Method: A standard 3-day regimen of artemether-lumefantrine was administered to each patient on steady-state efavirenz-based antiretroviral therapy (ART). Pharmacokinetic parameters were obtained from intensive plasma concentration-time data. Genotyping data were tested for compliance with Hardy-Weinberg equilibrium by Chi-square test. Linear regressions, Mann-Whitney U-test or Kruskal-Wallis tests were conducted to examine the association of lumefantrine plasma level with CYP2B6 c.516G>T, NR1I3 152c-1089T>C, CYP2B6 c.983T>C, CYP3A5*3 and CYP3A4*22. Results: Among a total of 69 malaria-HIV coinfected patients (34 nonpregnant and 35 pregnant), median (interquartile range) age was 33 (27-36.5) years and body weight was 59.5 (50-67.5) kg. In nonpregnant group, CYP2B6 c.516G>T was significantly associated with lower log Cday 7 of lumefantrine using multivariate linear regressions (β = -0.239; P = 0.013). In 59% of women with CYP2B6 c.516T, Cday 7 of lumefantrine was below the target of 280 ng/mL compared to 47% in the noncarriers. CYP2B6 c.983T>C significantly associated with higher log Cday 7 of Desbutyl Lumefantrine in both pregnant (β = 0.383; P = 0.033) and nonpregnant (β = 0.395; P = 0.023) groups. Composite genotypes for both CYP2B6 Single-nucleotide polymorphisms strongly associated with lumefantrine plasma concentration. An associative trend between lumefantrine pharmacokinetics and NR1I3 152c-1089T>C genotypes indicated that 70% of the Cday 7 of lumefantrine in those with NR1I3 152c-1089TT genotype was below 280 ng/mL compared to 53% in those with NR1I3 152c-1089CC or CT genotype. Conclusion: The findings revealed that the efavirenz-lumefantrine interaction was accentuated in the group with CYP2B6 c.516T, c.983C and NR1I3 152c-1089T alleles. This warrants further investigations of other drug-drug interactions for optimising dosing in genetically defined subgroups, particularly during drug development.
Effect of artemisinins and amino alcohol partner antimalarials on mammalian sarcoendoplasmic reticulum calcium adenosine triphosphatase activity
Basic Clin Pharmacol Toxicol 2008 Sep;103(3):209-13.PMID:18684232DOI:10.1111/j.1742-7843.2008.00256.x.
The aim of this study was to assess the ability of currently deployed antimalarials to inhibit mammalian sarcoendoplasmic reticulum calcium adenosine triphosphatase (SERCA). Artemisinins exert their antiplasmodial action by inhibiting parasite PfATP6, a SERCA enzyme, and possess neurotoxic potential; mefloquine is neurotoxic and inhibits mammalian SERCA, an orthologue of PfATP6. SERCA in rabbit muscle was tested in vitro for inhibition by artemisinin and amino alcohol antimalarials. Significant inhibition of mammalian SERCA, as mean difference from uninhibited, control values was seen with both enantiomers of mefloquine: (+)-mefloquine (10 microM: -35.83, 95% CI -59.63 to -12.03; 50 microM: -54.06, 95% CI -77.86 to -30.26); (-)-mefloquine (10 microM: -24.35, 95% CI -41.56 to -7.15; 50 microM: -58.42, 95% CI -75.62 to -41.22); lumefantrine (1 microM: -25.46, 95% CI -45.82 to -5.10; 5 microM -34.83, 95% CI -60.08 to -9.58; 10 microM: -25.80, 95% CI -51.05 to -0.55); desbutyl-lumefantrine (5 microM: -50.16, 95% CI -84.24 to -16.08); dihydroartemisinin (1 microM: -39.25, 95% CI -63.74 to -14.76; 5 microM: -39.30, 95% CI -64.88 to -13.72). Dihydroartemisinin in higher concentrations (10 microM) stimulated SERCA activity: (+40.90, 95% CI 11.37 to 70.44). No statistically significant inhibition was seen with artemether at 1, 5 and 10 microM. Equimolar combinations of artemether and lumefantrine or of dihydroartemisinin and lumefantrine, when studied at concentrations that inhibit SERCA individually, failed to show any inhibition. Dihydroartemisinin, mefloquine, lumefantrine and Desbutyl Lumefantrine inhibit mammalian SERCA at periphysiological concentrations, although the neurotoxicity of mefloquine is not wholly attributable to this property. Candidate antimalarials should be screened pre-clinically for SERCA inhibition.