EIDD 1931

Cas：3258-02-4

Product Information：

EIDD 1931 is a promising COVID-19 inhibitor. EIDD-1931 has broad spectrum antiviral activity against SARS-CoV-2, MERS-CoV, SARS-CoV, and related zoonotic group 2b or 2c Bat-CoVs, as well as increased potency against a coronavirus bearing resistance mutations to the nucleoside analog inhibitor remdesivir. In mice infected with SARS-CoV or MERS-CoV, both prophylactic and therapeutic administration of EIDD-2801, an orally bioavailable NHC-prodrug (β-D-N4-hydroxycytidine-5'-isopropyl ester), improved pulmonary function, and reduced virus titer and body weight loss. Decreased MERS-CoV yields in vitro and in vivo were associated with increased transition mutation frequency in viral but not host cell RNA, supporting a mechanism of lethal mutagenesis in CoV. The potency of NHC/EIDD-2801 against multiple coronaviruses and oral bioavailability highlight its potential utility as an effective antiviral against SARS-CoV-2 and other future zoonotic coronaviruses.EIDD-1931 is an active metabolite of EIDD-2801

Chemical Formula: C9H13N3O6

Exact Mass: 259.0804

Molecular Weight: 259.218

Elemental Analysis: C, 41.70; H, 5.06; N, 16.21; O, 37.03

Synonym:

EIDD-1931

EIDD 1931

EIDD1931

N4-Hydroxycytidine

β-D-N4-hydroxycytidine

Uridine

Chemical Name:

N4-Hydroxycytidine

InChi Key:

XCUAIINAJCDIPM-XVFCMESISA-N

InChi Code: InChI=1S/C9H13N3O6/c13-3-4-6(14)7(15)8(18-4)12-2-1-5(11-17)10-9(12)16/h1-2,4,6-8,13-15,17H,3H2,(H,10,11,16)/t4-,6-,7-,8-/m1/s1

Smiles Code:

OC[C@@H]1[C@H]([C@H]([C@H](N2C(N=C(C=C2)NO)=O)O1)O)O

Technical Data：

Appearance: Solid powder

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: >3 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

In Vitro：

Beta-d-N4-hydroxycytidine is an anti-VEEV (venezuelan equine encephalitis virus) agent with EC50, EC90, and EC99 are 0.426, 1.036, and 2.5 μM, respectively.

Beta-d-N4-hydroxycytidine inhibits CHIKV replicon activity and the 50% effective concentration (EC50) s 0.8 μM in the Huh-7–CHIKV replicon cell line. Similar results is presented with the replicon in BHK-21 cells (EC50=1.8 μM).

NHC has no cytotoxicity for NHC in the Huh-7 cell culture system until up to 100 μM using MTT assays. The 50% cytotoxic concentration (CCsub>50) values for NHC are determined to be 30.6 μM, 7.7 μM, and 2.5 μM in peripheral blood mononuclear (PBM), Vero, and CEM cells, respectively.

NHC behaves as a pyrimidine analog, NHC-mediated inhibition of the CHIKV replicon can be abrogated by the addition of exogenous nucleosides, such as pyrimidines C and U, but dA, dC, dG, dU, or T has no impact on the replicon. Pyrimidines A and G contributes to replicon inhibition both in the presence and in the absence of NHC.

References：

1. Sheahan TP, Sims AC, Zhou S, Graham RL, Pruijssers AJ, Agostini ML, Leist SR, Schäfer A, Dinnon KH 3rd, Stevens LJ, Chappell JD, Lu X, Hughes TM, George AS, Hill CS, Montgomery SA, Brown AJ, Bluemling GR, Natchus MG, Saindane M, Kolykhalov AA, Painter G, Harcourt J, Tamin A, Thornburg NJ, Swanstrom R, Denison MR, Baric RS. An orally bioavailable broad-spectrum antiviral inhibits SARS-CoV-2 in human airway epithelial cell cultures and multiple coronaviruses in mice. Sci Transl Med. 2020 Apr 6:eabb5883. doi: 10.1126/scitranslmed.abb5883. Epub ahead of print. PMID: 32253226.

2. Agostini ML, Pruijssers AJ, Chappell JD, Gribble J, Lu X, Andres EL, Bluemling GR, Lockwood MA, Sheahan TP, Sims AC, Natchus MG, Saindane M, Kolykhalov AA, Painter GR, Baric RS, Denison MR. Small-Molecule Antiviral β-d-N4-Hydroxycytidine Inhibits a Proofreading-Intact Coronavirus with a High Genetic Barrier to Resistance. J Virol. 2019 Nov 26;93(24):e01348-19. doi: 10.1128/JVI.01348-19. PMID: 31578288; PMCID: PMC6880162.

3. Toots M, Yoon JJ, Cox RM, Hart M, Sticher ZM, Makhsous N, Plesker R, Barrena AH, Reddy PG, Mitchell DG, Shean RC, Bluemling GR, Kolykhalov AA, Greninger AL, Natchus MG, Painter GR, Plemper RK. Characterization of orally efficacious influenza drug with high resistance barrier in ferrets and human airway epithelia. Sci Transl Med. 2019 Oct 23;11(515):eaax5866. doi: 10.1126/scitranslmed.aax5866. PMID: 31645453; PMCID: PMC6848974.

4. Painter GR, Bowen RA, Bluemling GR, DeBergh J, Edpuganti V, Gruddanti PR, Guthrie DB, Hager M, Kuiper DL, Lockwood MA, Mitchell DG, Natchus MG, Sticher ZM, Kolykhalov AA. The prophylactic and therapeutic activity of a broadly active ribonucleoside analog in a murine model of intranasal venezuelan equine encephalitis virus infection. Antiviral Res. 2019 Nov;171:104597. doi: 10.1016/j.antiviral.2019.104597. Epub 2019 Sep 5. PMID: 31494195.

Products are for research use only. Not for human use.