Foscarnet Sodium targets cytomegalovirus (CMV) DNA polymerase (EC50 = 120 μM for CMV AD169 strain) [1]
Foscarnet Sodium inhibits HIV-1 reverse transcriptase (IC50 = 45 μM) [2]
Foscarnet Sodium suppresses herpes simplex virus type 1 (HSV-1) DNA polymerase (EC50 = 80 μM) and HSV-2 DNA polymerase (EC50 = 95 μM) [2]

Influenza A Victoria (IC50=29 μM), influenza B HK (IC50=61 μM), avian influenza myeloblastosis virus (IC50=5-8 μM), HSV-1, etc. strains (IC50=0.4-3.5 μM) are all inhibited by foscarnet sodium (Trisodium phosphonoformate)[2].

---

Foscarnet Sodium inhibited CMV replication in human foreskin fibroblasts (HFF) with an EC50 of 120 μM, reducing viral plaque formation by 50% [1]
Foscarnet Sodium showed synergistic anti-CMV activity with ganciclovir in HFF cells, with a combination index (CI) of 0.6, resulting in 90% viral replication inhibition at combined concentrations of 60 μM (foscarnet) + 0.5 μM (ganciclovir) [1]
Foscarnet Sodium suppressed replication of acyclovir-resistant HSV-1 strains in Vero cells, with an EC50 of 110 μM [2]
Foscarnet Sodium exhibited low cytotoxicity in HFF and Vero cells, with CC50 values > 1000 μM, resulting in a selectivity index (SI) > 8 for CMV and > 10 for HSV [2]
Foscarnet Sodium directly inhibited viral DNA chain elongation by binding to the pyrophosphate-binding site of viral DNA polymerases, without requiring intracellular activation [2]

Foscarnet Sodium display an efficient therapy effect on animal with virus diseases, such as cutaneous infection, herpes keratitis, genital infection, or systemic and interacerebral infection. For example, Foscarnet Sodium (100 mM) applied at initiated 48 h post inoculation with twice daily applications of 30 μL for 4 days, displays a more than 70% reduction in cumulative score after inoculation with HSV-1 strain C42. Foscarnet Sodium (20 mg/kg) given as an aerosol to mice infected with murine CMV caused a reduction of 60% in lung titers.

---

Foscarnet Sodium reduced CMV viral load in the spleen and liver of CMV-infected mice by 1.8 log10 PFU/g tissue after intravenous administration of 60 mg/kg/day for 7 days [2]
Foscarnet Sodium improved survival rate of CMV-infected immunocompromised mice by 50% compared to untreated controls, when administered at 80 mg/kg/day (intraperitoneal) for 10 days [2]
Foscarnet Sodium suppressed HSV-1-induced skin lesions in guinea pigs, reducing lesion size by 60% at 40 mg/kg/day (intravenous) for 5 days [2]

CMV DNA polymerase inhibition assay: Prepare a reaction mixture containing recombinant CMV DNA polymerase, activated calf thymus DNA (template), deoxynucleotide triphosphates (dNTPs), and [3H]-dCTP. Incubate with serial dilutions of Foscarnet Sodium (10–500 μM) at 37°C for 90 min. Terminate the reaction with trichloroacetic acid, filter through glass fiber filters, and measure radioactivity to calculate the inhibition rate of DNA polymerase [2]
HIV-1 reverse transcriptase inhibition assay: Prepare a reaction system with recombinant HIV-1 reverse transcriptase, poly(rA)-oligo(dT) template-primer, and [3H]-dTTP. Add Foscarnet Sodium (5–200 μM) and incubate at 37°C for 60 min. Stop the reaction with EDTA, precipitate DNA with ethanol, and quantify radioactivity to determine IC50 [2]

CMV antiviral and synergistic cell assay: Seed HFF cells in 96-well plates at 2×104 cells/well and incubate until confluent. Infect with CMV (MOI = 0.1) for 2 h, then treat with Foscarnet Sodium alone (20–500 μM) or in combination with ganciclovir (0.1–5 μM) for 7 days. Stain cells with crystal violet to count viral plaques, calculate EC50 and combination index (CI) using the Chou-Talalay method [1]
HSV antiviral cell assay: Culture Vero cells in 96-well plates at 3×104 cells/well. Infect with acyclovir-resistant HSV-1 (MOI = 0.05) for 1 h, then add Foscarnet Sodium (30–1000 μM) and incubate for 48 h. Measure viral yield via plaque assay and assess cell viability using MTT assay to determine CC50 [2]

Dissolved in Water solution with 0.1% Tween 80 and 10% (wt/wt) glycerol and adjusted to pH 6.0; 5 mM; Topical application
Guinea-pigs with cutaneous HSV-1 infections on the backs

---

CMV-infected mouse model assay: Immunocompromised mice (nu/nu nude mice) are intraperitoneally infected with CMV (1×106 PFU/mouse). Two days post-infection, Foscarnet Sodium is administered via intravenous injection at 40, 60, or 80 mg/kg/day for 7–10 days. The drug is formulated in 0.9% saline. At study end, spleen and liver tissues are harvested to quantify viral load by plaque assay; survival rate is recorded daily [2]
HSV-induced skin lesion guinea pig assay: Female guinea pigs are inoculated with HSV-1 (1×105 PFU) on the shaved flank. One day post-inoculation, Foscarnet Sodium is given via intravenous injection at 20, 40, or 60 mg/kg/day for 5 days. Drug is dissolved in 0.9% saline. Lesion size is measured daily; viral load in lesion tissues is determined by plaque assay at study end [2]

Sodium phosphonoformate has low oral bioavailability in humans (< 20%) and requires intravenous administration to exert its systemic effects [2]. Sodium phosphonoformate is rapidly distributed after intravenous injection, with a volume of distribution (Vd) of 0.5–0.7 L/kg in humans [2]. The plasma elimination half-life (t1/2) of sodium phosphonoformate in humans is 3–6 hours [2]. Renal excretion is the main elimination route, with 80–90% of the administered dose excreted unchanged in the urine [2]. Sodium phosphonoformate has low plasma protein binding in humans (< 10%) [2].

Sodium phosphonoformate causes dose-dependent nephrotoxicity in humans, with 20-30% of patients experiencing elevated serum creatinine levels at therapeutic doses (60 mg/kg every 8 hours) [3]. Sodium phosphonoformate induces electrolyte disturbances (hypocalcemia, hypophosphatemia) in 15-25% of treated patients [3]. In vitro studies have shown that sodium phosphonoformate has no significant cytotoxicity to proximal tubular cells of normal human kidneys at concentrations ≤500 μM [2]. The LD50 of intravenously administered sodium phosphonoformate in mice is 1500 mg/kg [2]. Sodium phosphonoformate does not inhibit cytochrome P450 enzymes, therefore drug interactions are minimal [2].

[1]. Synergistic effect of ganciclovir and foscarnet on cytomegalovirus replication in vitro.Antimicrob Agents Chemother. 1990 Feb;34(2):373-5.

[2]. Antiviral effects of phosphonoformate (PFA, foscarnet sodium).Pharmacol Ther. 1982;19(3):387-415.

[3]. Moving Past Ganciclovir and Foscarnet: Advances in CMV Therapy.Curr Hematol Malig Rep. 2020 Jan 24.

Trisodium foscarnet is the trisodium salt of foscarnet. It is used as an antiviral drug to treat cytomegalovirus retinitis (CMV retinitis, an inflammation of the retina that can lead to blindness) and as an alternative to ganciclovir for HIV patients who require concurrent antiretroviral therapy but cannot tolerate ganciclovir due to blood toxicity. It is an antiviral drug. It is an organic sodium salt and a one-carbon compound. It contains a foscarnet ion. Sodium foscarnet is a prescription antiviral drug approved by the U.S. Food and Drug Administration (FDA) for the treatment of cytomegalovirus (CMV) retinitis in HIV patients. Sodium foscarnet is also approved by the FDA for the treatment of a specific type of herpes simplex virus infection called acyclovir-resistant mucocutaneous herpes simplex virus (HSV) infection in people with compromised immune systems. Cytomegalovirus (CMV) disease (such as retinitis affecting the eye) and HSV disease can be opportunistic infections (OIs) of HIV.
Sodium phosphonoformate is the trisodium salt of an inorganic pyrophosphate analog with antiviral activity. Sodium phosphonoformate selectively blocks the pyrophosphate binding site of herpesvirus-specific DNA polymerase without affecting the concentration of cellular DNA polymerase. The drug does not require phosphorylation by thymidine kinase (TK) or other kinases, and is therefore effective in vitro against herpes simplex virus (HSV) TK-deficient mutants and cytomegalovirus (CMV) UL97 mutants. Because sodium phosphonoformate can cross the blood-brain barrier, it can be used to treat viral infections of the central nervous system.
An antiviral drug used to treat cytomegalovirus retinitis. Sodium phosphonoformate is also active against human herpesvirus and HIV.
See also: Sodium phosphonoformate (containing the active moiety).

---

Sodium phosphonoformate is an inorganic pyrophosphate analog with broad-spectrum antiviral activity used to treat viral infections caused by herpesvirus and HIV[2].
Sodium phosphonoformate exerts its antiviral effect by directly binding to the pyrophosphate binding sites of viral DNA polymerase and reverse transcriptase, thereby blocking viral DNA synthesis[2].
Sodium phosphonoformate is indicated for the treatment of cytomegalovirus retinitis and acyclovir-resistant herpes simplex virus infection in immunocompromised patients (e.g., HIV-infected individuals)[3].
Unlike nucleoside analogues (e.g., ganciclovir, acyclovir), sodium phosphonoformate does not require intracellular phosphorylation to exert its effect. After activation, it is effective against nucleoside-resistant viral strains[2].
Sodium phosphonoformate was approved by the FDA in 1991 for the treatment of cytomegalovirus retinitis[3].

CNA3O5P

191.95

191.917

63585-09-1

Foscarnet trisodium hexahydrate;34156-56-4

44561

White to off-white solid powder

270-272°C

62-65 °C(lit.)

270-272°C

0

5

0

10

103

0

DFHAXXVZCFXGOQ-UHFFFAOYSA-K

InChI=1S/CH3O5P.3Na/c2-1(3)7(4,5)6/h(H,2,3)(H2,4,5,6)/q;3*+1/p-3

trisodium;phosphonatoformate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)