Tenofovir diphosphate
(Synonyms: 泰诺福韦二乙胺盐(异构体混合物),TFV-DP) 目录号 : GC60357
An HIV reverse transcriptase and HBV polymerase inhibitor
Cas No.:166403-66-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Tenofovir diphosphate is an inhibitor of HIV reverse transcriptase (Kis = 0.022 and 1.55 ?M for RNA and DNA, respectively) and hepatitis B virus (HBV) polymerase (Ki = 0.18 ?M).1,2 It is selective for these enzymes over DNA polymerase α and β, as well as mitochondrial DNA polymerase γ (Kis = 5.2, 81.7, and 59.5 ?M, respectively). Tenofovir diphosphate is formed intracellularly through phosphorylation of the prodrugs tenofovir and tenofovir disoproxil by nucleotide kinases.3 Increased levels of tenofovir diphosphate in isolated peripheral blood mononuclear cells (PBMCs) correlate with a decrease in the risk of simian HIV (SHIV) acquisition in a macaque model of rectal SHIV transmission.4
1.Cherrington, J.M., Allen, S.J.W., Bischofberger, N., et al.Kinetic interaction of the diphosphates of 9-(2-phosphonylmethoxyethyl)adenine and other anti-HIV active purine congeners with HIV reverse transcriptase and human DNA polymerases α, β and γAntivir. Chem. Chemother.6(4)217-221(1995) 2.Delaney, W.E., IV, Ray, A.S., Yang, H., et al.Intracellular metabolism and in vitro activity of tenofovir against hepatitis B virusAntimicrob. Agents Chemother.50(7)2471-2477(2006) 3.Robbins, B.L., Srinivas, R.V., Kim, C., et al.Anti-human immunodeficiency virus activity and cellular metabolism of a potential prodrug of the acyclic nucleoside phosphonate 9-R-(2-phosphonomethoxypropyl)adenine (PMPA), bis(isopropyloxymethylcarbonyl)PMPAAntimicrob. Agents Chemother.42(3)612-617(1998) 4.Anderson, P.L., Glidden, D.V., Bushman, L.R., et al.Tenofovir diphosphate concentrations and prophylactic effect in a macaque model of rectal simian HIV transmissionJ. Antimicrob. Chemother.69(9)2470-2476(2014)
| Cas No. | 166403-66-3 | SDF | |
| 别名 | 泰诺福韦二乙胺盐(异构体混合物),TFV-DP | ||
| Canonical SMILES | C[C@@H](OC[P](O[P](O[P](O)(O)=O)(O)=O)(O)=O)CN1C2=NC=NC(N)=C2N=C1 | ||
| 分子式 | C9H16N5O10P3 | 分子量 | 447.17 |
| 溶解度 | 储存条件 | ||
| 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 | 2.2363 mL | 11.1814 mL | 22.3629 mL |
| 5 mM | 0.4473 mL | 2.2363 mL | 4.4726 mL |
| 10 mM | 0.2236 mL | 1.1181 mL | 2.2363 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。
Immunoassay for HIV Drug Metabolites Tenofovir and Tenofovir diphosphate
ACS Infect Dis 2020 Jul 10;6(7):1635-1642.PMID:32392030DOI:10.1021/acsinfecdis.0c00010.
Poor patient adherence to antiretroviral medication represents a major obstacle for managing disease and reducing rates of new HIV infections. The measurement of patient drug levels is the most objective method of determining adherence. Tenofovir and Tenofovir diphosphate are metabolites of some of the most common HIV medications for treatment and prevention and can be quantified by mass spectrometry. Here, we report the development of a competitive enzyme linked immunoassay as a simplified approach for detecting tenofovir and Tenofovir diphosphate. Monoclonal antibodies were produced by two tenofovir-hapten conjugates and screened for binding to immobilized tenofovir, and then for competition by tenofovir and Tenofovir diphosphate. Antibody specificity was evaluated against adenosine phosphates, which are close structural analogs. We performed numerical simulations of reaction equilibrium to guide assay optimization. When used to evaluate spiked tenofovir in plasma and spiked Tenofovir diphosphate in red blood cell lysate, the optimized assay had high sensitivity and specificity.
Cumulative Tenofovir diphosphate exposure in persons with HIV taking single- vs. multiple-tablet regimens
Pharmacotherapy 2022 Aug;42(8):641-650.PMID:PMC9870651DOI:10.1002/phar.2711.
Background: We assessed cumulative antiretroviral exposure-using Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS)-in persons with HIV (PWH) receiving tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART) as single-tablet regimens (STR) or multiple-tablet regimens (MTR). Methods: Blood for DBS was prospectively collected in PWH on TDF during 1144 person visits (n = 523). Linear mixed-effects models, adjusted for baseline characteristics, were used to compare TFV-DP in STR versus MTR. Models adjusted for ART regimen using either anchor drug class, pharmacokinetic booster status (unboosted [u/] or boosted [b/]), or a combined STR/MTR and booster categorical variable. Results: In the anchor class-adjusted model, STR had 19% (95% confidence interval [CI]: 3%-37%; p = 0.02) higher TFV-DP concentrations than MTR. However, in the booster-adjusted model, STR was not significantly higher than MTR (estimate 5%, 95% CI: -9% to 21%; p = 0.48), although PWH on b/ART had 35% (95% CI: 16%-58%; p = 0.0001) higher TFV-DP than u/ART. In the STR/MTR-boosted variable model, when compared to u/MTR, b/STR, b/MTR, and u/STR had 25% (95% CI: 7%-47%; p = 0.005), 37% (95% CI: 17%-59%; p < 0.0001), and 7% (95% CI: -7% to 24%; p = 0.34) higher TFV-DP, respectively. Compared with b/MTR, b/STR had 9% (95% CI: -31% to 10%; p = 0.37) lower TFV-DP. In a sensitivity analysis of PWH with HIV viral load <20 copies/ml at all visits, b/STR and b/MTR had 34% (95% CI: 16%-55%; p < 0.0001) and 12% (95% CI: -2% to 27%; p = 0.09) higher TFV-DP, respectively, compared with u/MTR, while u/STR had 4% (95% CI: -15% to 8%; p = 0.50) lower TFV-DP. Compared with b/MTR, b/STR had 17% (95% CI: 2%-30%; p = 0.03) higher TFV-DP. Conclusions: Persons with HIV on b/TDF-based ART had higher TFV-DP than u/ART, regardless of STR or MTR use. No significant differences in TFV-DP between regimens of the same boosting status (i.e., b/STR vs. b/MTR; u/STR vs. u/MTR) were observed in the full cohort. Future research should examine the clinical utility of these findings in patient-tailored ART selection.
Cabotegravir for the prevention of HIV-1 in women: results from HPTN 084, a phase 3, randomised clinical trial
Lancet 2022 May 7;399(10337):1779-1789.PMID:35378077DOI:10.1016/S0140-6736(22)00538-4.
Background: Oral pre-exposure prophylaxis has been introduced in more than 70 countries, including many in sub-Saharan Africa, but women experience considerable barriers to daily pill-taking, such as stigma, judgement, and the fear of violence. Safe and effective long-acting agents for HIV prevention are needed for women. We aimed to evaluate the safety and efficacy of injectable cabotegravir compared with daily oral Tenofovir diphosphate plus emtricitabine (TDF-FTC) for HIV prevention in HIV-uninfected women. Methods: HPTN 084 was a phase 3, randomised, double-blind, double-dummy, active-controlled, superiority trial in 20 clinical research sites in seven countries in sub-Saharan Africa. Participants were eligible for enrolment if they were assigned female sex at birth, were aged 18-45 years, reported at least two episodes of vaginal intercourse in the previous 30 days, were at risk of HIV infection based on an HIV risk score, and agreed to use a long-acting reversible contraceptive method. Participants were randomly assigned (1:1) to either active cabotegravir with TDF-FTC placebo (cabotegravir group) or active TDF-FTC with cabotegravir placebo (TDF-FTC group). Study staff and participants were masked to study group allocation, with the exception of the site pharmacist who was responsible for study product preparation. Participants were prescribed 5 weeks of daily oral product followed by intramuscular injections every 8 weeks after an initial 4-week interval load, alongside daily oral pills. Participants who discontinued injections were offered open-label daily TDF-FTC for 48 weeks. The primary endpoints of the study were incident HIV infection in the intention-to-treat population, and clinical and laboratory events that were grade 2 or higher in all women who had received at least one dose of study product. This study is registered with ClinicalTrials.gov, NCT03164564. Findings: From Nov 27, 2017, to Nov 4, 2020, we enrolled 3224 participants (1614 in the cabotegravir group and 1610 in the TDF-FTC group). Median age was 25 years (IQR 22-30); 1755 (54·7%) of 3209 had two or more partners in the preceding month. 40 incident infections were observed over 3898 person-years (HIV incidence 1·0% [95% CI 0·73-1·40]); four in the cabotegravir group (HIV incidence 0·2 cases per 100 person-years [0·06-0·52]) and 36 in the TDF-FTC group (1·85 cases per 100 person-years [1·3-2·57]; hazard ratio 0·12 [0·05-0·31]; p<0·0001; risk difference -1·6% [-1·0% to -2·3%]. In a random subset of 405 TDF-FTC participants, 812 (42·1%) of 1929 plasma samples had tenofovir concentrations consistent with daily use. Injection coverage was 93% of the total number of person-years. Adverse event rates were similar across both groups, apart from injection site reactions, which were more frequent in the cabotegravir group than in the TDF-FTC group (577 [38·0%] of 1519 vs 162 [10·7%] of 1516]) but did not result in injection discontinuation. Confirmed pregnancy incidence was 1·3 per 100 person-years (0·9-1·7); no congenital birth anomalies were reported. Interpretation: Although both products for HIV prevention were generally safe, well tolerated, and effective, cabotegravir was superior to TDF-FTC in preventing HIV infection in women. Funding: National Institute of Allergy and Infectious Diseases, ViiV Healthcare, and the Bill & Melinda Gates Foundation. Additional support was provided through the National Institute of Mental Health, the National Institute on Drug Abuse, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. ViiV Healthcare and Gilead Sciences provided pharmaceutical support.
Tenofovir diphosphate in dried blood spots predicts future viremia in persons with HIV taking antiretroviral therapy in South Africa
AIDS 2022 Jun 1;36(7):933-940.PMID:PMC9167214DOI:10.1097/QAD.0000000000003185.
Objectives: Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is used as a biomarker of antiretroviral therapy (ART) adherence. Recent treatment studies have shown that TFV-DP predicts future viremia in persons with HIV (PWH) but there are few data from high-burden settings. We investigated whether TFV-DP in DBS predicts future viral breakthrough in South African PWH. Design: Prospective observational cohort. Methods: We enrolled 250 adults receiving tenofovir-containing regimens, currently virally suppressed (<50 copies/ml) but at risk of future viral breakthrough, from four primary health clinics in Cape Town. Paired viral load and DBS for TFV-DP were collected monthly for 12 months. Viral breakthrough was the first confirmed viral load greater than 400 copies/ml. Logistic regression estimated the odds ratio (OR) and 95% confidence intervals for future viral breakthrough at the next visit. Results: Participants provided 2944 paired DBS and viral load samples. Median (IQR) age was 34 (27-42) years; median duration on ART at study entry was 11 (4-12) months;78% were women. Twenty-one (8%) participants developed viral breakthrough. Participants with TFV-DP 400 fmol/punch or less had an adjusted OR of 16.1 (95% CI: 3.9-67.4; P < 0.001) for developing viral breakthrough 1 month later compared with participants with TFV-DP greater 800 fmol/punch. Conclusion: TFV-DP in DBS strongly predicted future viral breakthrough in a clinical cohort of South African PWH. A biomarker able to identify PWH at risk for future viral breakthrough has the potential to improve health outcomes through timely intervention. Future studies exploring the clinical use of TFV-DP in DBS in conjunction with viral load in ART monitoring are warranted.
Tenofovir diphosphate in Dried Blood Spots in Pregnant and Postpartum Women With HIV in Kenya: A Novel Approach to Measuring Peripartum Adherence
J Acquir Immune Defic Syndr 2022 Mar 1;89(3):310-317.PMID:34889866DOI:10.1097/QAI.0000000000002859.
Background: Adherence to antiretroviral therapy (ART) among pregnant and postpartum women with HIV (PWLWH) is critical to promote maternal health and prevent HIV transmission. Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is an objective assessment of cumulative ART adherence that has not been fully assessed in PWLWH. Setting: Southwestern Kenya. Methods: PWLWH receiving tenofovir disoproxil fumarate-based ART from 24 health facilities provided DBS samples at 3 time points [pregnancy/early postpartum (PP), 6 months PP, and 9-12 months PP]. Thresholds for daily adherence were defined as TFV-DP in DBS ≥650 fmol/punch in pregnancy and ≥950 PP. Descriptive analysis is presented. Cluster adjusted χ2 and t-tests were used to test for association with clinical and demographic factors. Results: A total of 419 DBS samples were collected from 150 PWLWH. Median TFV-DP in DBS was lowest, 552 fmol/punch [interquartile range (IQR), 395-759] in pregnancy and declined over time [914 (IQR, 644-1176) fmol/punch; early PP; 838 (IQR, 613-1063) fmol/punch 6 months PP; and 785 (IQR, 510-1009) fmol/punch 9-12 months; P < 0.001]. Only 42% of samples in pregnancy and 38.5% of samples in PP met thresholds for daily adherence. Clinical or demographic factors were not associated with suboptimal adherence levels. Conclusion: Cumulative ART exposure in PWLWH, quantified by TFV-DP in DBS, demonstrated a stepwise decrease (ie, adherence) PP. Most women demonstrated less than daily adherence throughout the peripartum period. Use of TFV-DP in DBS as a measure of cumulative ART adherence could help optimize health outcomes in PWLWH and their infants.