Islatravir

Source: Wikipedia, the free encyclopedia.
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]

Biological activity

Islatravir has activity against HIV in

animal models,[8] and is being studied clinically for HIV treatment and prophylaxis.[9] Islatravir is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) that unlike other such inhibitors, inhibits HIV through multiple mechanisms,[8] providing rapid suppression of the virus, when tested in macaques and mice.[10] Nevertheless, there are HIV strains resistant to islatravir and research is ongoing.[11][12]

References

  1. PMID 18487070
    .
  2. 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.
  8. ^
    PMID 24970894
    .
  9. ^ 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.
  10. PMID 25941222
    .
  11. ^ Bruno Marchand. "The Crystal Structure of EFdA‐Resistant HIV‐1 Reverse Transcriptase Reveals Structural Changes in the Polymerase Active Site" (PDF).
  12. PMID 27489345
    .
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