Tafenoquine Succinate (WR 238605 (Succinate))
(Synonyms: 他非诺喹琥珀酸盐; WR 238605 (Succinate)) 目录号 : GC32206
An antimalarial agent
Cas No.:106635-81-8
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
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. | 106635-81-8 | SDF | |
| 别名 | 他非诺喹琥珀酸盐; WR 238605 (Succinate) | ||
| Canonical SMILES | O=C(O)CCC(O)=O.CC(NC1=C2N=C(OC)C=C(C)C2=C(OC3=CC=CC(C(F)(F)F)=C3)C(OC)=C1)CCCN | ||
| 分子式 | C28H34F3N3O7 | 分子量 | 581.58 |
| 溶解度 | DMSO : 125 mg/mL (214.93 mM) | 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 | 1.7195 mL | 8.5973 mL | 17.1945 mL |
| 5 mM | 0.3439 mL | 1.7195 mL | 3.4389 mL |
| 10 mM | 0.1719 mL | 0.8597 mL | 1.7195 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。
Sporontocidal activity of the antimalarial WR-238605 against Plasmodium berghei ANKA in Anopheles stephensi
Am J Trop Med Hyg 1990 Mar;42(3):196-205.PMID:2180334DOI:10.4269/ajtmh.1990.42.196.
The influence of WR-238605 (8-[(4-amino-1-methyl-butyl) amino]-2,6-dimethoxy-4-methyl-5-[3-tri-fluoromethylphenoxyl] quinoline Succinate\) on the sporogonic development of a Plasmodium berghei ANKA clone was determined. Anopheles stephensi were fed on P. berghei infected mice treated 90 min earlier with 25 or 50 mg WR-238605/kg body weight. Mosquitoes engorging on drug-treated mice produced the same number of ookinetes as did those fed on controls; drug-fed mosquitoes produced fewer oocysts/mosquito than did controls. These oocytes developed more slowly than did those in control-fed mosquitoes. Sporozoites did not invade the salivary glands of drug-fed mosquitoes, nor did these mosquitoes transmit P. berghei to mice. Uptake of WR-238605 6 or 12 days after mosquitoes were infected with P. berghei had no effect on the percentage of mosquitoes with oocysts or the mean number of oocysts produced per mosquito. Oocyst development was significantly retarded in mosquitoes ingesting drug on day 6 postinfection. Subsequent salivary gland sporozoite infections were lighter in mosquitoes drug-fed on day 6 or day 12 than in control mosquitoes or mosquitoes drug-fed on day 18. These data indicate that WR-238605 has significant sporontocidal activity.
Simultaneous modeling of the pharmacokinetics and methemoglobin pharmacodynamics of an 8-aminoquinoline candidate antimalarial (WR 238605)
Pharm Res 1991 Dec;8(12):1505-10.PMID:1808614DOI:10.1023/a:1015842316177.
Methemoglobin (MHb) formation can be a clinically significant and dose-limiting side effect of 8-aminoquinoline antimalarials. MHb may also protect against cyanide poisoning. A two-compartment pharmacokinetic model, linked to a sigmoid Emax pharmacodynamic model, was developed to predict the MHb levels after administration of 8-[(4-amino-1-methylbutyl)amino]-2,6-dimethoxy-4-methyl-5-[(3- trifluoromethyl)phenoxy] quinoline succinate (WR 238605 Succinate\), a primaquine analogue. Six healthy male beagle dogs received four daily doses of 6.0 mg/kg (base) orally. Forty plasma drug concentrations and 19 MHb levels (effect) were determined over 7 weeks on each dog. Compartmental and noncompartmental pharmacokinetic and parametric and nonparametric pharmacodynamic analyses were performed. Model parameters (mean +/- SD) included a Vss/f of 18.5 +/- 2.8 L/kg, CL/f of 83 +/- 24 ml/hr/kg, terminal elimination t1/2 of 169.7 +/- 52.0 hr, t1/2keo of 123.0 +/- 22.4 hr, an Emax of 31.3 +/- 15.9% MHb, an EC50 of 596 +/- 128 ng/ml, and a sigmoidicity coefficient (n) of 1.94 +/- 0.47. The model was then validated in three additional dogs given three different dosing regimens. It predicted the peak plasma concentrations and MHb levels and the times of their occurrence well. This model could be useful for dose and sampling time selection in further animal studies and initial human phase I clinical testing.
Methemoglobin formation resulting from administration of candidate 8-aminoquinoline antiparasitic drugs in the dog
Fundam Appl Toxicol 1988 Feb;10(2):270-5.PMID:3356313DOI:10.1016/0272-0590(88)90311-9.
In vivo methemoglobin (MHb) formation caused by five 8-aminoquinoline compounds was tested in beagle dogs. Male beagle dogs were dosed orally once per day at 0.0116 mmol/kg for 4 consecutive days with primaquine (8-[4-amino-1-methylbutyl)amino]-6-methoxyquinoline, diphosphate), three candidate 8-aminoquinoline antimalarial drugs (WR 225,448 5-(3-trifluoromethyl)phenoxy-4-methyl primaquine, Succinate\); WR 238,605 2,6-dimethoxy-5-(3-trifluoromethyl)phenoxy-4-methyl primaquine, succinate; or WR 242,511 5-hexoxy-4-methyl primaquine, diphosphate dihydrate), or a candidate 8-aminoquinoline antileishmanial drug WR 6026 (8-[(6-diethylamino)amino]-6-methoxy-4-methyl quinoline, dihydrochloride). MHb and total hemoglobin levels were determined daily prior to dosing and for 29 days after drug administration. All compounds caused prolonged levels of MHb that peaked at Days 4 to 5 with disappearance half-lives of 5 to 9 days. Peak percentage MHb of primaquine, WR 6026, WR 238,605, WR 225,448, and WR 242,511 was 6.3, 20.7, 16.0, 25.3, and 48.1%, respectively. Total MHb as measured by area under the time-concentration curve was highest for WR 242,511, followed by WR 225,448, WR 238,605, WR 6026, and primaquine, respectively. The results of this study, in conjunction with other toxicity and efficacy studies, have been utilized to select one of these compounds for development as a replacement for the antimalarial drug primaquine, and also to characterize the MHb-forming properties of WR 6026.
Comparison of methemoglobin formers in protection against the toxic effects of cyanide
Gen Pharmacol 1992 Jan;23(1):19-25.PMID:1592224DOI:10.1016/0306-3623(92)90041-h.
1. Certain compounds that oxidize hemoglobin to methemoglobin (MHb) also protect against cyanide. 2. Evidence presented here suggests that other mechanisms may be involved. 3. Male Swiss ICR mice were pretreated intraperitoneally (i.p.) with various doses of primaquine phosphate (primaquine), WR6026 (6-methoxy-8-(6-diethylamino-hexylamino) lepidine dihydrochloride), WR238605 (8-[(4-amino-1-methylbutyl) amino]-2,6-dimethoxy-4-methyl-5-(3-trifluoromethylphenoxy) quinoline Succinate\), p-aminooctoyl-phenone (PAOP), or p-aminopropiophenone (PAPP). 4. The compounds were administered 15 or 60 min before an intramuscular (i.m.) challenge with a 2 x LD50 dose (5.0-5.6 mg/kg) of sodium cyanide (NaCN). 5. Twenty-four hr mortality was assessed and survivors were tested for motor incapacitation. 6. Primaquine, PAPP and PAOP increased survival compared to untreated controls, while the other MHb formers were not effective (P less than 0.05). 7. PAOP is believed to form sufficient MHb only after 3 to 4 hr after administration; however it was found to be effective when administered 15 min before NaCN challenge in this study. 8. This suggests that MHb formation may not be the only factor responsible for PAOP's anti-cyanide efficacy.