Tenofovir alafenamide fumarate
(Synonyms: 替诺福韦阿拉芬酰胺富马酸酯,GS-7340 (fumarate)) 目录号 : GC37758
Tenofovir alafenamide (TAF, GS-7340) fumarate is a prodrug of tenofovir but results in significantly higher intracellular tenofovir concentrations and lower serum levels. Tenofovir alafenamide is a novel nucleotide reverse transcriptase inhibitor for the treatment of HIV-1 infection.
Cas No.:379270-38-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.50%
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Tenofovir alafenamide (TAF, GS-7340) fumarate is a prodrug of tenofovir but results in significantly higher intracellular tenofovir concentrations and lower serum levels. Tenofovir alafenamide is a novel nucleotide reverse transcriptase inhibitor for the treatment of HIV-1 infection.
[1] Amanda K Gibson, et al. Ann Pharmacother. 2016 Nov;50(11):942-952.
| Cas No. | 379270-38-9 | SDF | |
| 别名 | 替诺福韦阿拉芬酰胺富马酸酯,GS-7340 (fumarate) | ||
| Canonical SMILES | NC1=NC=NC2=C1N=CN2C[C@@H](C)OC[P@](OC3=CC=CC=C3)(N[C@@H](C)C(OC(C)C)=O)=O.O=C(O)/C=C/C(O)=O | ||
| 分子式 | C25H33N6O9P | 分子量 | 592.54 |
| 溶解度 | DMSO: ≥ 36 mg/mL (60.76 mM); Water: ≥ 25 mg/mL (42.19 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 | 1.6876 mL | 8.4382 mL | 16.8765 mL |
| 5 mM | 0.3375 mL | 1.6876 mL | 3.3753 mL |
| 10 mM | 0.1688 mL | 0.8438 mL | 1.6876 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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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。
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Efficacy and safety of dolutegravir with emtricitabine and Tenofovir alafenamide fumarate or tenofovir disoproxil fumarate, and efavirenz, emtricitabine, and tenofovir disoproxil fumarate HIV antiretroviral therapy regimens started in pregnancy (IMPAACT 2010/VESTED): a multicentre, open-label, randomised, controlled, phase 3 trial
Lancet 2021 Apr 3;397(10281):1276-1292.PMID:33812487DOI:10.1016/S0140-6736(21)00314-7.
Background: Antiretroviral therapy (ART) during pregnancy is important for both maternal health and prevention of perinatal HIV-1 transmission; however adequate data on the safety and efficacy of different ART regimens that are likely to be used by pregnant women are scarce. In this trial we compared the safety and efficacy of three antiretroviral regimens started in pregnancy: dolutegravir, emtricitabine, and Tenofovir alafenamide fumarate; dolutegravir, emtricitabine, and tenofovir disoproxil fumarate; and efavirenz, emtricitabine, and tenofovir disoproxil fumarate. Methods: This multicentre, open-label, randomised controlled, phase 3 trial was done at 22 clinical research sites in nine countries (Botswana, Brazil, India, South Africa, Tanzania, Thailand, Uganda, the USA, and Zimbabwe). Pregnant women (aged ≥18 years) with confirmed HIV-1 infection and at 14-28 weeks' gestation were eligible. Women who had previously taken antiretrovirals in the past were excluded (up to 14 days of ART during the current pregnancy was permitted), as were women known to be pregnant with multiple fetuses, or those with known fetal anomaly or a history of psychiatric illness. Participants were randomly assigned (1:1:1) using a central computerised randomisation system. Randomisation was done using permuted blocks (size six) stratified by gestational age (14-18, 19-23, and 24-28 weeks' gestation) and country. Participants were randomly assigned to receive either once-daily oral dolutegravir 50 mg, and once-daily oral fixed-dose combination emtricitabine 200 mg and Tenofovir alafenamide fumarate 25 mg; once-daily oral dolutegravir 50 mg, and once-daily oral fixed-dose combination emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg; or once-daily oral fixed-dose combination of efavirenz 600 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg. The primary efficacy outcome was the proportion of participants with viral suppression, defined as an HIV-1 RNA concentration of less than 200 copies per mL, at or within 14 days of delivery, assessed in all participants with an HIV-1 RNA result available from the delivery visit, with a prespecified non-inferiority margin of -10% in the combined dolutegravir-containing groups versus the efavirenz-containing group (superiority was tested in a pre-planned secondary analysis). Primary safety outcomes, compared pairwise among treatment groups, were the occurrence of a composite adverse pregnancy outcome (ie, either preterm delivery, the infant being born small for gestational age, stillbirth, or spontaneous abortion) in all participants with a pregnancy outcome, and the occurrence of grade 3 or higher maternal and infant adverse events in all randomised participants. This trial was registered with ClinicalTrials.gov, NCT03048422. Findings: Between Jan 19, 2018, and Feb 8, 2019, we enrolled and randomly assigned 643 pregnant women: 217 to the dolutegravir, emtricitabine, and Tenofovir alafenamide fumarate group, 215 to the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group, and 211 to the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group. At enrolment, median gestational age was 21·9 weeks (IQR 18·3-25·3), the median HIV-1 RNA concentration among participants was 902·5 copies per mL (152·0-5182·5; 181 [28%] of 643 participants had HIV-1 RNA concentrations of <200 copies per mL), and the median CD4 count was 466 cells per μL (308-624). HIV-1 RNA concentrations at delivery were available for 605 (94%) participants. Of these, 395 (98%) of 405 participants in the combined dolutegravir-containing groups had viral suppression at delivery compared with 182 (91%) of 200 participants in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (estimated difference 6·5% [95% CI 2·0 to 10·7], p=0·0052; excluding the non-inferiority margin of -10%). Significantly fewer participants in the dolutegravir, emtricitabine, and Tenofovir alafenamide fumarate group (52 [24%] of 216) had a composite adverse pregnancy outcome than those in the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group (70 [33%] of 213; estimated difference -8·8% [95% CI -17·3 to -0·3], p=0·043) or the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (69 [33%] of 211; -8·6% [-17·1 to -0·1], p=0·047). The proportion of participants or infants with grade 3 or higher adverse events did not differ among the three groups. The proportion of participants who had a preterm delivery was significantly lower in the dolutegravir, emtricitabine, and Tenofovir alafenamide fumarate group (12 [6%] of 208) than in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (25 [12%] of 207; -6·3% [-11·8 to -0·9], p=0·023). Neonatal mortality was significantly higher in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group (ten [5%] of 207 infants) than in the dolutegravir, emtricitabine, and Tenofovir alafenamide fumarate group (two [1%] of 208; p=0·019) or the dolutegravir, emtricitabine, and tenofovir disoproxil fumarate group (three [2%] of 202; p=0·050). Interpretation: When started in pregnancy, dolutegravir-containing regimens had superior virological efficacy at delivery compared with the efavirenz, emtricitabine, and tenofovir disoproxil fumarate regimen. The dolutegravir, emtricitabine, and Tenofovir alafenamide fumarate regimen had the lowest frequency of composite adverse pregnancy outcomes and of neonatal deaths. Funding: National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health.
Tenofovir alafenamide fumarate
Antivir Ther 2022 Apr;27(2):13596535211067600.PMID:35499175DOI:10.1177/13596535211067600.
Tenofovir alafenamide fumarate is a lipophilic prodrug of tenofovir which is preferentially metabolized in lymphatic tissue resulting in high concentrations of tenofovir (TFV) and its active diphosphate metabolite inside the cells that replicate HIV. Due to its selectivity for these tissues, lower total doses of TAF can be administered relative to tenofovir disoproxil fumarate (TDF) which results in improved bone and renal biomarkers. Tenofovir alafenamide fumarate has become the "backbone" of multiple combination products for the treatment of HIV, combined with emtricitabine for PreP and as a monotherapy for the treatment or HBV.
Tenofovir alafenamide fumarate for the treatment of HIV infection
Drugs Today (Barc) 2016 Nov;52(11):617-625.PMID:28112280DOI:10.1358/dot.2016.52.11.2546852.
Tenofovir alafenamide fumarate is a recently developed prodrug of tenofovir, a nucleotide analogue reverse transcriptase inhibitor with potent inhibitory activity against HIV. The utility of a previously developed tenofovir prodrug, tenofovir disoproxil fumarate, had been hampered by renal and bone mineral adverse events. Tenofovir alafenamide fumarate overcomes the shortcomings of tenofovir disoproxil fumarate by delivering high intracellular concentrations of the parent drug, tenofovir, while substantially reducing systemic exposure. Tenofovir alafenamide fumarate is currently available as a component of three fixed-dose products: i) coformulation with emtricitabine; ii) coformulation with elvitegravir, cobicistat and emtricitabine; and iii) coformulation with rilpivirine and emtricitabine.
Evaluating the combination of emtricitabine/ Tenofovir alafenamide fumarate to reduce the risk of sexually acquired HIV-1-infection in at-risk adults
Expert Opin Pharmacother 2021 Jul;22(10):1245-1251.PMID:33691554DOI:10.1080/14656566.2021.1902504.
Introduction: Pre-exposure prophylaxis with a single daily pill of emtricitabine (F) plus tenofovir disoproxil fumarate (TDF) is highly efficacious at preventing HIV acquisition. Tenofovir alafenamide (TAF) is another tenofovir prodrug that delivers higher intracellular levels of active tenofovir diphosphate in blood cells and has an improved safety profile compared to TDF. Given the recent regulatory approval of the F/TAF combination for prophylaxis, it is important to review its safety and efficacy. Areas covered: In this review, the author examines the safety and efficacy of F/TAF for pre-exposure prophylaxis. Both published manuscripts and conference papers are reviewed. F/TAF is non-inferior to F/TDF at preventing HIV acquisition in men and transgender women with a trend toward superiority. F/TAF has yet to be tested against HIV exposure via injection or vaginal intercourse. Expert opinion: Within these limitations, F/TAF may be particularly advantageous for older individuals thanks to improved kidney safety compared to F/TDF. F/TAF did not possess the hypolipidemic properties of F/TDF and was associated with weight gains.