4′-Ethynyl-2-fluoro-2′-deoxyadenosine

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4′-Ethynyl-2-fluoro-2′-deoxyadenosine
EFdA.svg
Names
IUPAC name
2'-Deoxy-4'-ethynyl-2-fluoroadenosine
Other names
EFdA; MK-8591
Identifiers
3D model (JSmol)
ChemSpider
UNII
Properties
C12H12FN5O3
Molar mass 293.26 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

4′-Ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) is a nucleoside analog that has been shown to potently inhibit HIV replication.[1]

Biological activity[edit]

EFdA has activity against HIV in animal models,[2] and is being studied clinically for HIV treatment and prophylaxis.[3] EFdA is a nucleoside analog reverse transcriptase inhibitor that unlike other such inhibitors, inhibits HIV through multiple mechanisms.[2] providing rapid suppression of the virus, when tested in macaques and mice.[4] Nevertheless, there are HIV strains resistant to EFdA and research is ongoing.[5]

References[edit]

  1. ^ Kawamoto, A; Kodama, E; Sarafianos, SG; Sakagami, Y; Kohgo, S; Kitano, K; Ashida, N; Iwai, Y; Hayakawa, H; Nakata, H; Mitsuya, H; Arnold, E; Matsuoka, M (2008). "2'-deoxy-4'-C-ethynyl-2-halo-adenosines active against drug-resistant human immunodeficiency virus type 1 variants". The International Journal of Biochemistry & Cell Biology. 40 (11): 2410–20. doi:10.1016/j.biocel.2008.04.007. PMID 18487070. 
  2. ^ a b Michailidis, Eleftherios; Huber, Andrew D.; Ryan, Emily M.; Ong, Yee T.; Leslie, Maxwell D.; Matzek, Kayla B.; Singh, Kamalendra; Marchand, Bruno; Hagedorn, Ariel N.; Kirby, Karen A.; Rohan, Lisa C.; Kodama, Eiichi N.; Mitsuya, Hiroaki; Parniak, Michael A.; Sarafianos, Stefan G. (2014). "4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) Inhibits HIV-1 Reverse Transcriptase with Multiple Mechanisms". Journal of Biological Chemistry. 289 (35): 24533–48. doi:10.1074/jbc.M114.562694. PMC 4148878Freely accessible. PMID 24970894. 
  3. ^ Grobler, Jay (February 22–25, 2016). Long-Acting Oral and Parenteral Dosing of MK-8591 for HIV Treatment or Prophylaxis. Boston, Massachusetts. Conference on Retroviruses and Opportunistic Infections. 98. 
  4. ^ Stoddart, Cheryl A.; Galkina, Sofiya A.; Joshi, Pheroze; Kosikova, Galina; Moreno, Mary E.; Rivera, Jose M.; Sloan, Barbara; Reeve, Aaron B.; Sarafianos, Stefan G.; Murphey-Corb, Michael; Parniak, Michael A. (2015). "Oral Administration of the Nucleoside EFdA (4′-Ethynyl-2-Fluoro-2′-Deoxyadenosine) Provides Rapid Suppression of HIV Viremia in Humanized Mice and Favorable Pharmacokinetic Properties in Mice and the Rhesus Macaque". Antimicrobial Agents and Chemotherapy. 59 (7): 4190–8. doi:10.1128/AAC.05036-14. PMC 4468726Freely accessible. PMID 25941222. 
  5. ^ Bruno Marchand. "The Crystal Structure of EFdA‐Resistant HIV‐1 Reverse Transcriptase Reveals Structural Changes in the Polymerase Active Site" (PDF).