Tenofovir Disoproxil Fumarate

Catalog No.S1400 Synonyms: GS-1278 Disoproxil Fumarate

Tenofovir Disoproxil Fumarate Chemical Structure

Molecular Weight(MW): 635.51

Tenofovir Disoproxil Fumarate belongs to a class of antiretroviral drugs, it inhibits the activity of HIV reverse transcriptase by competing with the natural substrate deoxyadenosine 5’-triphosphate and, after incorporation into DNA, by DNA chain termination.

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In DMSO USD 130 In stock
USD 97 In stock
USD 310 In stock
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  • Human PBMCs containing indicated concentrations of Tenofovir disoproxil fumarate were inoculated with 5 ng mock-exposed or semen-exposed R5-HIV-luciferase, or 50 ng R5-HIV-luciferase as infectivity matched control. Infection rates were determined 3 days post inoculation.

    Sci Transl Med, 2014, 6(262): 262ra157 . Tenofovir Disoproxil Fumarate purchased from Selleck.

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Biological Activity

Description Tenofovir Disoproxil Fumarate belongs to a class of antiretroviral drugs, it inhibits the activity of HIV reverse transcriptase by competing with the natural substrate deoxyadenosine 5’-triphosphate and, after incorporation into DNA, by DNA chain termination.
Targets
HIV reverse transcriptase [1]
(Cell-free assay)
In vitro

Tenofovir is eliminated from systemic circulation renally through a combination of glomerular filtration and active tubular secretion. Tenofovir is not a substrate for human organic cation transporter type 1 (hOCT1) or hOCT2. Tenofovir accumulates to fivefold lower levels in MRP4-overexpressing cells, and its accumulation could be increased by an MRP inhibitor. [1] Tenofovir produces no significant changes in mitochondrial DNA (mtDNA) levels in human hepatoblastoma (HepG2) cells, skeletal muscle cells (SkMCs), or renal proximal tubule epithelial cells. Tenofovir elevates lactate production by less than 20% in HepG2 cells or SkMCs. [2] Tenofovir is efficiently phosphorylated to tenofovir diphosphate (TFV-DP) in both HepG2 cells and primary human hepatocytes. Tenofovir has a 50% effective concentration of 1.1 mM against HBV in cell-based assays, and potency is improved > 50-fold by the addition of bis-isoproxil progroups. Tenofovir has previously demonstrated full activity against lamivudine-resistant HBV in vitro and clinically. [3] Tenofovir inhibits the proliferation of liver-derived HepG2 cells and normal skeletal muscle cells with CC(50) values of 398 mM and 870 mM, respectively. Tenofovir shows substantially weaker effects on proliferation and viability of renal proximal tubule epithelial cells than cidofovir, a related nucleotide analog with the potential to induce renal tubular dysfunction. [4]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
MT2 cells MVXGeY5kfGmxbjDhd5NigQ>? MV:1JIRigXN? NUnpbmE6UW6qaXLpeIlwdiCxZjD2bZJ2ey2rbnT1Z4VlKGO7dH;wZZRpcWNiZX\m[YN1KGmwIIfpcIQhfHmyZTDITXYhO2FiaX7m[YN1\WRiTWSyJINmdGy|IHHmeIVzKDViZHH5d{whTUN3ME2wMlAyPSEQvF2= MXOxO|U3OjN4Nh?=
MT2 cells MlPnSpVv[3Srb36gZZN{[Xl? MnO2RY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGlXOSCrbn\lZ5Rm\CCrbjDoeY1idiCPVEKgZ4VtdHNiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iC4aYLhcEBz\XCuaXPheIlwdixiSVO1NF0xNjV2IN88US=> NXvaWphwOTl3OU[4PFU>
human bone marrow cells M1z6ZWN6fG:2b4jpZ:Kh[XO|YYm= NVTYS5BpOjRiaB?= NU\Nc3pUS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4h[m:wZTDtZZJzd3diY3XscJMh[W[2ZYKgNlQhcHK|IHL5JGJHXS2HIHHzd4F6NCCFQ{WwQVAvQSEQvF2= MmTwNlA1Ozl4MEm=
human HepG2 cells NW\kXpBiS3m2b4TvfIlkyqCjc4PhfS=> MXi5JIRigXN? MYjDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDI[ZBIOiClZXzsd{Bi\nSncjC5JIRigXNiYomgUXRVKGG|c3H5MEBKSzVyPUKuN|Eh|ryP NFHhU4MyPzh6OE[2Ni=>
human HeLa P4/R5 cells Mo[zSpVv[3Srb36gZZN{[Xl? NG\IZ5pCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBJUVZzIHnu[oVkfGWmIHnuJIh2dWGwIFjlUIEhWDRxUkWgZ4VtdHNiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iC4aYLhcEBz\XCuaXPheIlwdixiSVO1NF01NjdizszN NX[0WoprOTl3OU[4PFU>
human HeLa P4/R5 cells M3XKOGZ2dmO2aX;uJIF{e2G7 M{XhPGFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXjFiaHHyZo9zcW6pIILleoVze2VidILhcpNkemmydHHz[UBMPjWUIH31eIFvfCCrbn\lZ5Rm\CCrbjDoeY1idiCKZVzhJHA1N1J3IHPlcIx{KGG|c3Xzd4VlKGG|IHnubIljcXSrb36gc4Yhfmm{YXygdoVxdGmlYYTpc44tKEmFNUC9NVEvPCEQvF2= M{TsTlE6PTl4OEi1
human HeLaT4 cells Mk[4R5l1d3SxeHnjxsBie3OjeR?= NIOxRpBEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBJ\UyjVESgZ4VtdHNiYomgW3NVNTFiYYPzZZktKEOFNUC9N|Qh|ryP M{LUSFIyODZyMUC4

... Click to View More Cell Line Experimental Data

Protocol

Cell Research:

[5]

+ Expand
  • Cell lines: VK2 cells
  • Concentrations: 450 μM or 1,350 μM
  • Incubation Time: 15 min to 12 h
  • Method:

    VK2 cells were exposed to TDF (90 μM or 450 μM) and TFV (450 μM or 1,350 μM) in serum-free RPMI 1640 at 37°C for 15 min to 12 h. At different times postexposure, cells were washed with ice-cold PBS and metabolites were extracted overnight in 70% (vol/vol) methanol, followed by centrifugation at 18,000 × g for 10 min at 4°C. 


    (Only for Reference)
Animal Research:

[6]

+ Expand
  • Animal Models: BALB/c mice
  • Formulation: 50 mM trisodium citrate dihydrate
  • Dosages: 50, 500, or 1000 mg/kg
  • Administration: oral administration
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 100 mg/mL (157.35 mM)
Ethanol 44 mg/mL (69.23 mM)
Water Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 635.51
Formula

C19H30N5O10P.C4H4O4

CAS No. 202138-50-9
Storage powder
in solvent
Synonyms GS-1278 Disoproxil Fumarate

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03032536 Recruiting Hepatitis B|Chronic Hepatitis B|Viral Hepatitis B Alios Biopharma Inc. January 31, 2017 Phase 1
NCT03048422 Not yet recruiting HIV Infections National Institute of Allergy and Infectious Diseases (NIAID) April 30, 2017 Phase 3
NCT03043326 Recruiting HIV Prevention Asociación Civil Impacta Salud y Educación, Peru|Gilead Sciences January 23, 2017 --
NCT02454764 Not yet recruiting HBV Institute of Liver and Biliary Sciences, India May 2017 --
NCT02937779 Not yet recruiting Hepatitis B Chronic Infection|Pregnancy French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS) April 2017 Phase 4
NCT02995005 Not yet recruiting Hepatitis B Johns Hopkins Bloomberg School of Public Health|Thrasher Research Fund|Shoklo Malaria Research Unit|Chiang Mai University March 2017 --

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Reverse Transcriptase Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID