Tenofovir alafenamide fumarate

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Tenofovir alafenamide fumarate
Tenofovir alafenamide fumarate.svg
Systematic (IUPAC) name
(S)-Isopropyl-2-(((S)-((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)(phenoxy)phosphoryl)amino)propanoate
Clinical data
Legal status
?
Identifiers
CAS number 379270-37-8
ATC code ?
UNII FWF6Q91TZO YesY
Chemical data
Formula C21H29N6O5P 
Mol. mass 476.19 g/mol

Tenofovir alafenamide fumarate (TAF) (formerly GS-7340) is a nucleotide reverse transcriptase inhibitor and a novel prodrug of tenofovir. It is under development by Gilead Sciences for use in the treatment of HIV infection. Closely related to the commonly used reverse-transcriptase inhibitor tenofovir disoproxil fumarate (Viread), TAF has greater antiviral activity and better distribution into lymphoid tissues than that agent.[1][2]

Gilead has announced a phase 3 clinical trial evaluating a single-tablet regimen combining GS-7340 with cobicistat, emtricitabine and elvitegravir[3] and plans to coformulate the drug with cobicistat, emtricitabine and the protease inhibitor darunavir.[4][5][6] In a 48 week study comparing Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate, the results showed the prodrug to be non inferior to the established agent, but at much lower dosages and with lower incidence of adverse side effects such as impaired kidney function.[7][8][9]

References[edit]

  1. ^ Eisenberg, E. J.; He, G. X.; Lee, W. A. (2001). "Metabolism of Gs-7340, A Novel Phenyl Monophosphoramidate Intracellular Prodrug of Pmpa, in Blood". Nucleosides, Nucleotides and Nucleic Acids 20 (4–7): 1091–1098. doi:10.1081/NCN-100002496. PMID 11562963.  edit
  2. ^ M Markowitz, A Zolopa, et al. GS-7340 Demonstrates Greater Declines in HIV-1 RNA than Tenofovir Disoproxil Fumarate During 14 Days of Monotherapy in HIV-1 Infected Subjects. 18th Conference on Retroviruses and Opportunistic Infections 2 Mar 2011. Paper # 152LB
  3. ^ "Gilead Initiates Phase 3 Clinical Program for Tenofovir Alafenamide" (Press release). Gilead. January 2013. 
  4. ^ McQueen, Courtney (16 Nov 2011). "Gilead And Tibotec To Develop Single-Pill Protease Inhibitor-Based Combination Regimen". The AIDS Beacon. 
  5. ^ GS-7340 Packs Greater HIV Punch, Potentially Better Safety, Versus Viread Horn, Tim. 15 Mar 2012. AIDSmeds.com
  6. ^ Pharmacokinetics of a Novel EVG/COBI/FTC/GS-7340 Single Tablet Regimen. 13th International Workshop on Clinical Pharmacology of HIV Therapy. Barcelona, Spain. April 16-18, 2012.
  7. ^ Once-Daily Tenofovir Prodrug Combo Pill as Effective as Stribild. AIDSmeds.com 1 Nov 2012.
  8. ^ CROI 2013: New Pro-drug Tenofovir Alafenamide Appears Equally Effective but Better Tolerated. Highleyman, Liz. HIVandHepatitis.com. 6 March 2013.
  9. ^ Horn, T. et al. Tenefovir Alafenamide Fumarate (TAF) Sign-On Letter to Gilead. 13 June 2013. Treatment Action Group.