Islatravir

Islatravir
Names
IUPAC name
2′-Deoxy-4′-ethynyl-2-fluoroadenosine
Systematic IUPAC name
(2R,3S,5R)-5-(6-Amino-2-fluoro-9H-purin-9-yl)-2-ethynyl-2-(hydroxymethyl)oxolan-3-ol
Other names
EFdA; MK-8591; 4′-Ethynyl-2-fluoro-2′-deoxyadenosine
Identifiers
3D model (JSmol)
ChemSpider
UNII
  • 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
  • C#C[C@]1([C@H](C[C@@H](O1)n2cnc3c2nc(nc3N)F)O)CO
Properties
C12H12FN5O3
Molar mass 293.258 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Islatravir (4′-ethynyl-2-fluoro-2′-deoxyadenosine, EFdA, or MK-8591) is an investigational drug for the treatment of HIV infection.[1] It is classified as a nucleoside reverse transcriptase translocation inhibitor (NRTTI).[2] Merck is developing a subdermal drug-eluting implant to administer islatravir.[3][4]

In 2021, FDA placed a partial clinical hold for several studies under Islatravir.[5] The reason was a decline in CD4 T cells under therapy. Merck announced to restart the study program in 2023 with a decreased dose, however studies of islatravir for pre-exposure prophylaxis (PrEP) will be discontinued.[6]

In 2024, results from a phase II study combining islatravir with lenacapavir indicated that the regimen shows promise as a possible weekly oral regimen.[7]

  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. ^ Roy M. Gulick (2018). "Investigational Antiretroviral Drugs: What is Coming Down the Pipeline". Top Antivir Med. 25 (4): 127–132. PMC 5935216. PMID 29689540.
  3. ^ "Someday, an Arm Implant May Prevent H.I.V. Infection for a Year". New York Times. July 23, 2019.
  4. ^ "Merck Presents Early Evidence on Extended Delivery of Investigational Anti-HIV-1 Agent Islatravir (MK-8591) via Subdermal Implant" (Press release). July 23, 2019.
  5. ^ "Merck restarts islatravir HIV treatment studies, but abandons monthly PrEP". aidsmap.com. Retrieved 2023-05-02.
  6. ^ "Merck to Initiate New Phase 3 Clinical Program with Lower Dose of Daily Oral Islatravir in Combination with Doravirine for Treatment of People with HIV-1 Infection". Merck. Retrieved 10 March 2024.
  7. ^ Highleyman, Liz (6 March 2024). "Islatravir plus lenacapavir could be the first once-weekly oral HIV treatment". Aidsmap. Retrieved 10 March 2024.