| Size | Price | Stock | Qty |
|---|---|---|---|
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| 1g |
|
||
| 2g |
|
||
| Other Sizes |
|
Purity: ≥98%
Tenofovir Alafenamide fumarate (formerly also known as TAF and GS-7340) is a novel prodrug of tenofovir, which is a potent reverse transcriptase inhibitor [nucleotide reverse transcriptase inhibitor (NRTIs)], it is used for the treatment of HIV and Hepatitis B. By blocking reverse transcriptase, Tenofovir Alafenamide prevent HIV from multiplying and can reduce the amount of HIV in the body. Tenofovir alafenamide is a prodrug that it is inactive in the parent form, and has to be converted to tenofovir diphosphate (TFV-DP) in vivo.
| Targets |
HIV-1/2 nucleotide reverse transcriptase
|
|---|---|
| ln Vitro |
Tenofovir alafenamide fumarate (GS-7340 fumarate) exhibited comparable antiviral activity across all cell types, with a CC50 ranging from 4.7 to 42 μM for MT-4 and MT-2 cells, respectively. The fumarate varied from 5 to 7 nM. A panel of HIV-1 and HIV-2 isolates, comprising HIV-1 M group A to G subtypes and group N and O isolates, were used to assess TAF's antiviral activity. The average EC50 of 3.5 nM was found for TAF among the 29 main HIV-1 isolates tested in PBMC, while the average EC50 of 11.8 nM was found for AZT, the internal control. The average EC50 for AZT was 6.4 nM and for TAF was 1.8 nM for HIV-2 isolates [2].
|
| ln Vivo |
The amidate prodrug of tenofovir is called GS-7340 fumarate, or tenofovir alafenamide fumarate. It has better plasma stability and good oral bioavailability when compared to tenofovir disoproxil fumarate (TDF) [1].
|
| Enzyme Assay |
Intestinal and Hepatic S9 Stability[1]
GS-7340 was incubated at 10 μM with either dog or human intestinal and hepatic S9 fractions for 120 min at 37 °C in a 96-well plate format. At specified time points following compound addition, samples were quenched with 9 volumes of an aqueous solution containing 25% acetonitrile and 50% methanol. Plates were centrifuged at 3000g for 30 min, and 10 μL of the resulting solution was analyzed by LC–MS/MS. Data (analyte to internal standard peak area ratio) were plotted on a semi log scale and fitted using an exponential fit. Assuming first order kinetics, the half-life and rate of metabolism were determined. Predicted hepatic extraction was calculated from the half-life by reported methods using the well-stirred model for hepatic clearance.[1] Plasma Stability[1] GS-7340 was incubated at 2 μM in either dog or human plasma for 4 h at 37 °C. At specified time points, an aliquot from the incubation was quenched by addition of 9 volumes of 100% acetonitrile and internal standard. Following the last collection, samples were centrifuged at 3000g for 30 min and supernatants were transferred to a new plate containing an equal volume of water for analysis by liquid chromatography coupled to triple quadrupole mass spectrometry (LC–MS/MS). |
| Cell Assay |
Caco-2 Permeability[1]
Bidirectional permeability studies were done using confluent monolayers of the human colon carcinoma cell line caco-2 seeded in 12-well plates as previously reported. The effects of either concentration (10, 100, or 1,000 μM) or efflux transporter inhibition on the permeation of GS-7340 were studied. Effect of the inhibition of efflux transporters including P-glycoprotein (Pgp) was assessed following a 30 min preincubation of cell monolayers with 10 μM cyclosporin A (CsA) in transport buffer to allow for saturation of transporter binding sites. Following preincubation, fresh assay buffer containing CsA and GS-7340 was added and the assay was started. Each determination was performed in duplicate, and the permeability of control compounds (atenolol, propranolol, and digoxin) was determined to meet acceptance criteria for each batch of assay plates. |
| Animal Protocol |
Animals[1]
Male beagle dogs between the ages of 6 and 18 months were used for the in life portion of this study. The animals were housed in accordance with the standards of the American Association for Accreditation of Laboratory Animal Care and were receiving a standard commercial diet. Animals were handled in strict accordance with the Guide for the Care and Use of Laboratory Animals, and the protocol was reviewed by the Institutional Animal Care and Use Committee at SRI International. Animals were between 7 and 11 kg at dosing.[1] Drug Administration[1] For intravenous administration, GS-7340 was formulated in 5% dextrose in water. For oral administration, GS-7340 was formulated in 50 mM citric acid (pH 5.0) at doses of 2 to 10 mg/kg. For the 20 mg/kg dose, GS-7340 was formulated in 50 mM citric acid (pH 5.5) with 0.1% Polysorbate 20. To test the effect of efflux transport inhibition, dogs were administered 2 mg/kg GS-7340 1 h following pretreatment with a 75 mg capsule of CsA.[1] Plasma and PBMC Sample Collection[1] Blood (approximately 0.5 mL) was collected at specified time points over 24 h from the jugular vein (intraportal vein infusion and oral pharmacokinetic studies), the jugular and portal veins (oral administration to portal vein cannulated dogs), or the cephalic vein (jugular vein infusion). Plasma was isolated in Vacutainer tubes containing EDTA as an anticoagulant by centrifugation. At select time points (1, 4, 8, and 24 h postdose) in the 5 mg/kg oral pharmacokinetic study, 8 to 10 mL of blood was collected into Vacutainer cell preparation tubes (Becton Dickinson) for isolation of peripheral blood mononuclear cells (PBMC) and processed following manufacturer instructions. Small aliquots (10 μL) of isolated PBMC pellets diluted in 0.9% NaCl were maintained at room temperature and used to determine cell count. 500 μL of 70% methanol was added to the remaining PBMC pellets and, together with plasma samples, stored at −80 °C until shipment for further processing and analysis. |
| References |
|
| Additional Infomation |
Tenofovir alafenamide is an antiviral prescription medicine approved by the U.S. Food and Drug Administration (FDA) for the treatment of chronic hepatitis B virus infection (HBV) in adults and children 6 years of age and older who weigh at least 55 lb (25 kg) and who meet certain requirements, as determined by a health care provider.
HBV can be an opportunistic infection (OI) of HIV. Drug Indication Vemlidy is indicated for the treatment of chronic hepatitis B (CHB) in adults and paediatric patients 6 years of age and older weighing at least 25 kg (see section 5. 1). |
| Molecular Formula |
C25H33N6O9P
|
|---|---|
| Molecular Weight |
593.55
|
| Exact Mass |
592.204
|
| Elemental Analysis |
C, 50.68; H, 5.61; N, 14.18; O, 24.30; P, 5.23
|
| CAS # |
379270-38-9
|
| Related CAS # |
Tenofovir alafenamide;379270-37-8; 379270-38-9 (fumarate); 1392275-56-7 (hemifumarate);
|
| PubChem CID |
68516365
|
| Appearance |
White to off-white solid powder
|
| LogP |
3.656
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
14
|
| Rotatable Bond Count |
14
|
| Heavy Atom Count |
41
|
| Complexity |
799
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
[P@](C([H])([H])O[C@]([H])(C([H])([H])[H])C([H])([H])N1C([H])=NC2=C(N([H])[H])N=C([H])N=C12)(N([H])[C@]([H])(C(=O)OC([H])(C([H])([H])[H])C([H])([H])[H])C([H])([H])[H])(=O)OC1C([H])=C([H])C([H])=C([H])C=1[H].O([H])C(/C(/[H])=C(\[H])/C(=O)O[H])=O
|
| InChi Key |
MEJAFWXKUKMUIR-WIUYAKJJSA-N
|
| InChi Code |
InChI=1S/C21H29N6O5P.C4H4O4/c1-14(2)31-21(28)16(4)26-33(29,32-17-8-6-5-7-9-17)13-30-15(3)10-27-12-25-18-19(22)23-11-24-20(18)27;5-3(6)1-2-4(7)8/h5-9,11-12,14-16H,10,13H2,1-4H3,(H,26,29)(H2,22,23,24);1-2H,(H,5,6)(H,7,8)/b;2-1+/t15-,16+,33?;/m1./s1
|
| Chemical Name |
(S)-isopropyl 2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)amino)propanoate fumarate
|
| Synonyms |
GS734; GS-734; GS 734; GS 7340; GS-7340; GS7340; TAF; Tenofovir alafenamide fumarate; GS-7340 fumarate; 379270-38-9; GS-7340 monofumarate; H2S5S51WW6; GS-7340 (fumarate); GS-7339 monofumarate; L-Alanine, N-((S)-(((1R)-2-(6-amino-9H-purin-9-yl)-1-methylethoxy)methyl)phenoxyphosphinyl)-, 1-methylethyl ester, (2E)-2-butenedioate (1:1); trade name: Genvoya.
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ≥ 36 mg/mL (~60.76 mM)
H2O : ≥ 25 mg/mL (~42.19 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 6.67 mg/mL (11.26 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6848 mL | 8.4239 mL | 16.8478 mL | |
| 5 mM | 0.3370 mL | 1.6848 mL | 3.3696 mL | |
| 10 mM | 0.1685 mL | 0.8424 mL | 1.6848 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA