4′-Ethynyl-2-fluoro-2′-deoxyadenosine

4′-Ethynyl-2-fluoro-2′-deoxyadenosine
Names
	IUPAC name 2'-Deoxy-4'-ethynyl-2-fluoroadenosine
	Other names EFdA; MK-8591
Identifiers
CAS Number	865363-93-5;
3D model (JSmol)	Interactive image;
ChemSpider	4983885;
PubChem CID	6483431;
UNII	QPQ082R25D;
	InChI InChI=1S/C12H12FN5O3/c1-2-12(4-19)6(20)3-7(21-12)18-5-15-8-9(14)16-11(13)17-10(8)18/h1,5-7,19-20H,3-4H2,(H2,14,16,17)/t6-,7+,12+/m0/s1 Key: IKKXOSBHLYMWAE-QRPMWFLTSA-N;
	SMILES C#C[C@]1([C@H](C[C@@H](O1)n2cnc3c2nc(nc3N)F)O)CO;
Properties
Chemical formula	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

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

↑ 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.
1 2 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 4148878. PMID 24970894.
↑ 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.
↑ 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 4468726. PMID 25941222.
↑ Bruno Marchand. "The Crystal Structure of EFdA‐Resistant HIV‐1 Reverse Transcriptase Reveals Structural Changes in the Polymerase Active Site" (PDF).

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[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.

[Michailidis-2] 1 2 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 4148878. 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 4468726. PMID 25941222.

[5] Bruno Marchand. "The Crystal Structure of EFdA‐Resistant HIV‐1 Reverse Transcriptase Reveals Structural Changes in the Polymerase Active Site" (PDF).