Tafenoquine (WR 238605)
(Synonyms: 他非诺喹; WR 238605) 目录号 : GC32314
An antimalarial agent
Cas No.:106635-80-7
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
Tafenoquine is an aminoquinoline antimalarial agent.1 It is active against multidrug-resistant clinical isolates of P. falciparum (IC50s = 64.6-110.4 ng/ml). Tafenoquine (25 or 50 mg/kg) inhibits sporozoite transmission to mosquitos fed on P. berghei-infected mice.2 It also suppresses parasitemia in a hamster model of B. microti infection when administered at doses ranging from 3.25 to 52 mg/kg.3
1.Ohrt, C., Willingmyre, G.D., Lee, P., et al.Assessment of azithromycin in combination with other antimalarial drugs against Plasmodium falciparum in vitroAntimicrob. Agents Chemother.46(8)2518-2524(2002) 2.Coleman, R.E.Sporontocidal activity of the antimalarial WR-238605 against Plasmodium berghei ANKA in Anopheles stephensiAm. J. Trop. Med. Hyg.42(3)196-205(1990) 3.Marley, S.E., Eberhard, M.L., Steurer, F.J., et al.Evaluation of selected antiprotozoal drugs in the Babesia microti-hamster modelAntimicrob. Agents Chemother.41(1)91-94(1997)
| Cas No. | 106635-80-7 | SDF | |
| 别名 | 他非诺喹; WR 238605 | ||
| Canonical SMILES | CC1=CC(OC)=NC2=C1C(OC3=CC=CC(C(F)(F)F)=C3)=C(OC)C=C2NC(CCCN)C | ||
| 分子式 | C24H28F3N3O3 | 分子量 | 463.49 |
| 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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| 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 | 2.1575 mL | 10.7877 mL | 21.5754 mL |
| 5 mM | 0.4315 mL | 2.1575 mL | 4.3151 mL |
| 10 mM | 0.2158 mL | 1.0788 mL | 2.1575 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。
Glucose-6-phosphate dehydrogenase deficiency
Blood 2020 Sep 10;136(11):1225-1240.PMID:32702756DOI:10.1182/blood.2019000944.
Glucose 6-phosphate dehydrogenase (G6PD) deficiency is 1 of the commonest human enzymopathies, caused by inherited mutations of the X-linked gene G6PD. G6PD deficiency makes red cells highly vulnerable to oxidative damage, and therefore susceptible to hemolysis. Over 200 G6PD mutations are known: approximately one-half are polymorphic and therefore common in various populations. Some 500 million persons with any of these mutations are mostly asymptomatic throughout their lifetime; however, any of them may develop acute and sometimes very severe hemolytic anemia when triggered by ingestion of fava beans, by any of a number of drugs (for example, primaquine, rasburicase), or, more rarely, by infection. Approximately one-half of the G6PD mutations are instead sporadic: rare patients with these mutations present with chronic nonspherocytic hemolytic anemia. Almost all G6PD mutations are missense mutations, causing amino acid replacements that entail deficiency of G6PD enzyme activity: they compromise the stability of the protein, the catalytic activity is decreased, or a combination of both mechanisms occurs. Thus, genotype-phenotype correlations have been reasonably well clarified in many cases. G6PD deficiency correlates remarkably, in its geographic distribution, with past/present malaria endemicity: indeed, it is a unique example of an X-linked human polymorphism balanced through protection of heterozygotes from malaria mortality. Acute hemolytic anemia can be managed effectively provided it is promptly diagnosed. Reliable diagnostic procedures are available, with point-of-care tests becoming increasingly important where primaquine and its recently introduced analog Tafenoquine are required for the elimination of malaria.
Advances and roadblocks in the treatment of malaria
Br J Clin Pharmacol 2022 Feb;88(2):374-382.PMID:32656850DOI:10.1111/bcp.14474.
The deployment of artesunate for severe malaria and the artemisinin combination therapies (ACTs) for uncomplicated malaria has been a major advance in antimalarial therapeutics. These drugs have reduced treated mortality, accelerated recovery and reduced treatment failure rates and transmission from the treated infection. Artemisinin derivatives remain highly effective against falciparum malaria in most malaria endemic areas, but significant resistance has emerged in the Greater Mekong subregion of Southeast Asia. Resistance to artemisinins was followed by resistance to the ACT partner drugs, and fit multidrug resistant parasite lineages have now spread widely across the region. ACTs remain highly effective against P. vivax and the other malaria species. Recent studies have shown that radical curative regimens of primaquine (to prevent relapse) can be shortened to 7 days, and that the newly introduced single dose Tafenoquine is an alternative, although the currently recommended dose is insufficient in Southeast Asia and Oceania. Targeted malaria elimination using focal mass treatments with dihydroartemisinin-piperaquine have proved safe and effective malaria elimination accelerators, but progress overall towards malaria elimination is slow. Indeed since 2015 overall malaria case numbers globally have risen. As new drugs will not become widely available in the near future, active measures to preserve the current antimalarials should be given the highest priority.
Drugs in Development for Malaria
Drugs 2018 Jun;78(9):861-879.PMID:29802605DOI:10.1007/s40265-018-0911-9.
The last two decades have seen a surge in antimalarial drug development with product development partnerships taking a leading role. Resistance of Plasmodium falciparum to the artemisinin derivatives, piperaquine and mefloquine in Southeast Asia means new antimalarials are needed with some urgency. There are at least 13 agents in clinical development. Most of these are blood schizonticides for the treatment of uncomplicated falciparum malaria, under evaluation either singly or as part of two-drug combinations. Leading candidates progressing through the pipeline are artefenomel-ferroquine and lumefantrine-KAF156, both in Phase 2b. Treatment of severe malaria continues to rely on two parenteral drugs with ancient forebears: artesunate and quinine, with sevuparin being evaluated as an adjuvant therapy. Tafenoquine is under review by stringent regulatory authorities for approval as a single-dose treatment for Plasmodium vivax relapse prevention. This represents an advance over standard 14-day primaquine regimens; however, the risk of acute haemolytic anaemia in patients with glucose-6-phosphate dehydrogenase deficiency remains. For disease prevention, several of the newer agents show potential but are unlikely to be recommended for use in the main target groups of pregnant women and young children for some years. Latest predictions are that the malaria burden will continue to be high in the coming decades. This fact, coupled with the repeated loss of antimalarials to resistance, indicates that new antimalarials will be needed for years to come. Failure of the artemisinin-based combinations in Southeast Asia has stimulated a reappraisal of current approaches to combination therapy for malaria with incorporation of three or more drugs in a single treatment under consideration.
A new primaquine analogue, Tafenoquine (WR 238605), for prophylaxis against Plasmodium falciparum malaria
Clin Infect Dis 2001 Dec 15;33(12):1968-74.PMID:11700577DOI:10.1086/324081.
We tested Tafenoquine (WR 238605), a new long-acting 8-aminoquinoline, for its ability to prevent malaria in an area that is holoendemic for Plasmodium falciparum. In a double-blinded, placebo-controlled, randomized clinical trial in western Kenya, adult volunteers received a treatment course of 250 mg halofantrine per day for 3 days, to effect clearance of preexisting parasites. The volunteers were then assigned to 1 of 4 drug regimens: placebo throughout; 3 days of 400 mg (base) of tafenoquine per day, followed by placebo weekly; 3 days of 200 mg of tafenoquine per day, followed by 200 mg per week; and 3 days of 400 mg of tafenoquine per day, followed by 400 mg per week. Prophylaxis was continued for up to 13 weeks. Of the evaluable subjects (223 of 249 randomized subjects), volunteers who received 400 mg tafenoquine for only 3 days had a protective efficacy of 68% (95% confidence interval [CI], 53%-79%), as compared with placebo recipients; those who received 200 mg per day for 3 days followed by 200 mg per week had a protective efficacy of 86% (95% CI, 73%-93%); and those who received 400 mg for 3 days followed by 400 mg per week had a protective efficacy of 89% (95% CI, 77%-95%). A similar number of volunteers in the 4 treatment groups reported adverse events. Prophylactic regimens of 200 mg or 400 mg of tafenoquine, taken weekly for < or =13 weeks, are highly efficacious in preventing falciparum malaria and are well tolerated.
Measurement of Tafenoquine (WR 238605) in human plasma and venous and capillary blood by high-pressure liquid chromatography
Ther Drug Monit 2000 Apr;22(2):184-9.PMID:10774631DOI:10.1097/00007691-200004000-00008.
A simple, rapid, and accurate high-pressure liquid chromatographic method with fluorescence detection is described for the measurement of tafenoquine (TQ) (also known as WR 238605) from human plasma and venous and capillary blood. Tafenoquine was measured in plasma and venous blood following protein precipitation. Chromatographic separation was achieved using a Waters S5P Spherisorb phenyl analytical cartridge (150 mm x 4.6 mm I.D., 5 microm particle size) (Waters, Milford, MA, USA) and a mobile phase of 22 mM ammonium acetate, pH 4:acetonitrile (45:55, vol/vol). The flow rate was 1.5 mL/min and the retention times were approximately 3.5 min for WR VIIIAc (internal standard) and approximately 7.8 min for TQ. The interday and intraday coefficients of variation of TQ over a concentration range of 20-1000 ng/mL in plasma were < or =8.4% and in venous blood were < or =9.6%. The mean percent difference between added concentration and obtained concentration was 7.3% in plasma and 8.5% in venous blood over the corresponding concentration range. The limit of quantitation for both fluids was 10 ng/mL. Tafenoquine concentrations were comparable between capillary and venous blood with no significant difference between measurement in both biological fluids. The clinical application of the method was demonstrated by measuring plasma and whole blood concentrations of TQ from participants in a chemosuppression trial of the drug against malaria infections in Thailand.