Synonym
MK-8591; MK 8591; MK8591; Islatravir; EFdA
IUPAC/Chemical Name
(2R,3S,5R)-5-(6-amino-2-fluoro-9H-purin-9-yl)-2-ethynyl-2-(hydroxymethyl)tetrahydrofuran-3-ol
InChi Key
IKKXOSBHLYMWAE-QRPMWFLTSA-N
InChi Code
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
SMILES Code
NC1=C(N=CN2[C@H]3C[C@@H]([C@@](O3)(C#C)CO)O)C2=NC(F)=N1
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Islatravir (MK-8591) is a potent anti-HIV-1 agent, acting as a nucleoside reverse transcriptase inhibitor, with EC50s of 0.068 nM, 3.1 nM and 0.15 nM for HIV-1 (WT), HIV-1 (M184V), HIV-1 (MDR), respectively.
In vitro activity:
At 72 h, ISL (islatravir) and TDF (tenofovir disoproxil fumarate) inhibited cell growth in S2 cells by about 70–80% compared to the control (Fig. 1). This study examined the effect of drug concentration using S2 cells at 72 h. Cytotoxicity was observed in a concentration-dependent manner in ISL-treated and TDF-treated cells (Fig. 2). CC50 (50% cytotoxic concentration) was about 31.3 μM for ISL, 80.6 μM for TDF, and uncountable for TFV (Table 1).
Reference: J Pharmacol Sci. 2021 Jun;146(2):82-87. https://pubmed.ncbi.nlm.nih.gov/33941324/
In vivo activity:
EFdA treatment also resulted in significantly lower levels of HIV-DNA in the GI tract of EFdA-treated mice (p = 0.04, mean: 728 copies/105 cells, range: 20–1412 copies/105 cells) compared to untreated mice (mean: 4361 copies/105 cells, range: 801–7992 copies/105 cells) (Fig 5D). Together, these results demonstrate the strong ability of EFdA to control HIV replication in the GI tract.
Reference: PLoS One. 2016 Jul 20;11(7):e0159517. https://pubmed.ncbi.nlm.nih.gov/27438728/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
100.0 |
341.00 |
| Water |
3.6 |
12.17 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
293.26
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Kaneko M, Reien Y, Morio H, Fukuuchi T, Kaneko K, Hirayama Y, Hashimoto H, Kuwata N, Mitsuya H, Anzai N. Effects of islatravir (4'-ethynyl-2-fluoro-2'-deoxyadenosine or EFdA) on renal tubular cells and islatravir's interactions with organic anion transporters. J Pharmacol Sci. 2021 Jun;146(2):82-87. doi: 10.1016/j.jphs.2021.03.004. Epub 2021 Mar 19. PMID: 33941324.
2. Wu VH, Smith RA, Masoum S, Raugi DN, Ba S, Seydi M, Grobler JA, Gottlieb GS; University of Washington–Dakar HIV-2 Study Group. MK-8591 (4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine) Exhibits Potent Activity against HIV-2 Isolates and Drug-Resistant HIV-2 Mutants in Culture. Antimicrob Agents Chemother. 2017 Jul 25;61(8):e00744-17. doi: 10.1128/AAC.00744-17. PMID: 28559249; PMCID: PMC5527656.
3. Shanmugasundaram U, Kovarova M, Ho PT, Schramm N, Wahl A, Parniak MA, Garcia JV. Efficient Inhibition of HIV Replication in the Gastrointestinal and Female Reproductive Tracts of Humanized BLT Mice by EFdA. PLoS One. 2016 Jul 20;11(7):e0159517. doi: 10.1371/journal.pone.0159517. PMID: 27438728; PMCID: PMC4954669.
In vitro protocol:
1. Kaneko M, Reien Y, Morio H, Fukuuchi T, Kaneko K, Hirayama Y, Hashimoto H, Kuwata N, Mitsuya H, Anzai N. Effects of islatravir (4'-ethynyl-2-fluoro-2'-deoxyadenosine or EFdA) on renal tubular cells and islatravir's interactions with organic anion transporters. J Pharmacol Sci. 2021 Jun;146(2):82-87. doi: 10.1016/j.jphs.2021.03.004. Epub 2021 Mar 19. PMID: 33941324.
2. Wu VH, Smith RA, Masoum S, Raugi DN, Ba S, Seydi M, Grobler JA, Gottlieb GS; University of Washington–Dakar HIV-2 Study Group. MK-8591 (4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine) Exhibits Potent Activity against HIV-2 Isolates and Drug-Resistant HIV-2 Mutants in Culture. Antimicrob Agents Chemother. 2017 Jul 25;61(8):e00744-17. doi: 10.1128/AAC.00744-17. PMID: 28559249; PMCID: PMC5527656.
In vivo protocol:
1. Shanmugasundaram U, Kovarova M, Ho PT, Schramm N, Wahl A, Parniak MA, Garcia JV. Efficient Inhibition of HIV Replication in the Gastrointestinal and Female Reproductive Tracts of Humanized BLT Mice by EFdA. PLoS One. 2016 Jul 20;11(7):e0159517. doi: 10.1371/journal.pone.0159517. PMID: 27438728; PMCID: PMC4954669.
1: Sun L, Chavez-Eng C, Fillgrove KL, Lu B, Xie I, Rudd DJ, Breidinger S, Anderson M, Yeh S, Zhang R, Woolf EJ. Toward highly sensitive and reproducible LC-MS/MS analysis of MK-8591 phosphorylated anabolites in human peripheral blood mononuclear cells. Bioanalysis. 2019 Feb 15. doi: 10.4155/bio-2018-0101. [Epub ahead of print] PubMed PMID: 30767560.
2: Takamatsu Y, Das D, Kohgo S, Hayashi H, Delino NS, Sarafianos SG, Mitsuya H, Maeda K. The High Genetic Barrier of EFdA/MK-8591 Stems from Strong Interactions with the Active Site of Drug-Resistant HIV-1 Reverse Transcriptase. Cell Chem Biol. 2018 Oct 18;25(10):1268-1278.e3. doi: 10.1016/j.chembiol.2018.07.014. Epub 2018 Aug 30. PubMed PMID: 30174310; PubMed Central PMCID: PMC6261781.
3: Wu VH, Smith RA, Masoum S, Raugi DN, Ba S, Seydi M, Grobler JA, Gottlieb GS; University of Washington–Dakar HIV-2 Study Group. MK-8591 (4'-Ethynyl-2-Fluoro-2'-Deoxyadenosine) Exhibits Potent Activity against HIV-2 Isolates and Drug-Resistant HIV-2 Mutants in Culture. Antimicrob Agents Chemother. 2017 Jul 25;61(8). pii: e00744-17. doi: 10.1128/AAC.00744-17. Print 2017 Aug. PubMed PMID: 28559249; PubMed Central PMCID: PMC5527656.
