| Size | Price | Stock | Qty |
|---|---|---|---|
| 250mg |
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| 500mg |
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| 1g |
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| 5g |
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| Other Sizes |
| Targets |
Ganciclovir mono-O-acetate targets viral DNA polymerase, specifically the DNA polymerase of cytomegalovirus (CMV) and other herpesviruses. As a nucleoside analogue, ganciclovir is first phosphorylated by viral kinases to ganciclovir monophosphate, which is then further phosphorylated by cellular kinases to the active triphosphate form. Ganciclovir triphosphate competes with deoxyguanosine triphosphate (dGTP) for incorporation into viral DNA. Once incorporated, it acts as a chain terminator, preventing further elongation of the viral DNA strand and inhibiting viral DNA replication. The compound shows selectivity for viral DNA polymerase over cellular DNA polymerases, contributing to its antiviral activity and reduced host cell toxicity.
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| ln Vitro |
Ganciclovir mono-o-acetate is an ester of ganciclovir that is mono-O-acetate.
In vitro, ganciclovir mono-O-acetate is converted to ganciclovir, which demonstrates potent antiviral activity against CMV and other herpesviruses. The compound inhibits viral replication in infected cells, with EC50 values typically in the micromolar range for CMV. Ganciclovir shows activity against both laboratory strains and clinical isolates of CMV. The compound is more potent than acyclovir against CMV but less potent against herpes simplex virus (HSV). In vitro studies have demonstrated that ganciclovir inhibits viral DNA synthesis and reduces viral yield in infected cell cultures. Resistance to ganciclovir can arise through mutations in the viral kinase (UL97) or DNA polymerase (UL54) genes. |
| ln Vivo |
In vivo, ganciclovir mono-O-acetate is a prodrug that is converted to ganciclovir, which has demonstrated efficacy in animal models of CMV infection. The compound reduces viral load and improves survival in immunocompromised animals infected with CMV. Ganciclovir is the standard of care for the treatment and prophylaxis of CMV infections in transplant recipients and other immunocompromised patients. The mono-O-acetate derivative may offer improved oral bioavailability compared to ganciclovir, which has poor oral absorption. In vivo studies have shown that ganciclovir is effective in preventing CMV disease and reducing the incidence of CMV-related complications in high-risk patients.
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| Enzyme Assay |
In vitro enzyme assays for ganciclovir mono-O-acetate typically involve measuring the inhibition of viral DNA polymerase activity. The assay uses purified viral DNA polymerase (e.g., CMV DNA polymerase) and a DNA template-primer. The incorporation of radiolabeled nucleotides into the growing DNA chain is measured in the presence of varying concentrations of ganciclovir triphosphate (the active form). The inhibition of polymerase activity is expressed as the IC50. For selectivity assessment, the compound is tested against cellular DNA polymerases (e.g., human DNA polymerase α). The assay includes positive controls (known polymerase inhibitors) and negative controls (vehicle only). All reactions are performed in triplicate.
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| Cell Assay |
In vitro cell-based assays for ganciclovir mono-O-acetate are performed using CMV-susceptible cell lines such as human foreskin fibroblasts (HFF) or MRC-5 cells. Cells are infected with CMV (e.g., AD169 strain) at a multiplicity of infection (MOI) of 1-5. After viral adsorption, the cells are treated with serial dilutions of the compound (typically 0.1-100 μM) for 5-7 days. Viral replication is assessed by plaque reduction assay, by measuring viral DNA by qPCR, or by quantifying viral antigens by immunofluorescence or ELISA. The EC50 (concentration reducing viral replication by 50%) is determined. Cytotoxicity is assessed using MTT or neutral red uptake assays to determine the CC50 and selectivity index (SI = CC50/EC50).
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| Animal Protocol |
In vivo animal studies with ganciclovir mono-O-acetate are conducted in murine models of CMV infection, typically using mouse CMV (MCMV) as a surrogate for human CMV. Immunocompromised mice (e.g., SCID or immunosuppressed BALB/c) are infected with MCMV, and the compound is administered orally or intraperitoneally, typically at doses of 10-100 mg/kg/day. Viral load in target organs (e.g., liver, spleen, lungs) is measured by plaque assay or qPCR. Survival is monitored as a primary endpoint. Histopathological analysis is performed to assess organ damage. The efficacy of ganciclovir mono-O-acetate is compared to ganciclovir and vehicle controls. Pharmacokinetic sampling may be performed to establish exposure-response relationships.
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| ADME/Pharmacokinetics |
Ganciclovir mono-O-acetate is designed to improve the oral bioavailability of ganciclovir. Ganciclovir itself has poor oral bioavailability (approximately 5-10%) due to its low lipophilicity and poor membrane permeability. The mono-O-acetate derivative is a prodrug that is more lipophilic and may be better absorbed from the gastrointestinal tract. After absorption, the acetate ester is hydrolyzed to release active ganciclovir. The pharmacokinetic properties of ganciclovir include a half-life of 2-4 hours, renal excretion (primarily unchanged), and dose-dependent accumulation. The compound is metabolized minimally, and its pharmacokinetics are affected by renal function. Dosage adjustment is required in patients with renal impairment.
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| Toxicity/Toxicokinetics |
Ganciclovir and its derivatives have well-characterized toxicity profiles. The major dose-limiting toxicity is bone marrow suppression, leading to neutropenia, thrombocytopenia, and anemia. Gastrointestinal effects include nausea, vomiting, and diarrhea. Neurological toxicity, including confusion and seizures, can occur with high doses. Nephrotoxicity is also a concern, particularly in patients with pre-existing renal impairment. Ganciclovir is contraindicated in patients with severe hypersensitivity to the drug or its components. The compound is teratogenic and embryotoxic in animal studies and is contraindicated in pregnancy. Ganciclovir mono-O-acetate, as a research chemical, should be handled with appropriate safety precautions, including the use of personal protective equipment.
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| References |
[1]. Faulds D, et al. Ganciclovir. A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in cytomegalovirus infections. Drugs. 1990;39(4):597-638.
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| Additional Infomation |
Ganciclovir mono-O-acetate is a derivative of ganciclovir, which was first approved in the 1980s as a treatment for CMV retinitis in AIDS patients. Ganciclovir remains the standard of care for CMV infections in immunocompromised patients, including transplant recipients, HIV/AIDS patients, and those receiving immunosuppressive therapy. The drug is available in intravenous, oral, and intravitreal formulations. However, the poor oral bioavailability of ganciclovir has led to the development of prodrugs such as valganciclovir, which is the L-valyl ester of ganciclovir with significantly improved oral bioavailability. Ganciclovir mono-O-acetate is a research compound that may offer an alternative approach to improving ganciclovir's oral absorption. The compound is for research use only and not for human therapeutic applications.
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| Molecular Formula |
C11H15N5O5
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|---|---|
| Molecular Weight |
297.27
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| Exact Mass |
297.107
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| CAS # |
88110-89-8
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| PubChem CID |
135459820
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| Appearance |
White to light yellow solid powder
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| Density |
1.7±0.1 g/cm3
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| Boiling Point |
607.8ºC at 760 mmHg
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| Melting Point |
194-197ºC
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| Flash Point |
321.4ºC
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| Index of Refraction |
1.692
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| LogP |
-1.5
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
21
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| Complexity |
443
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1C2N=CN(C=2NC(N)=N1)COC(COC(C)=O)CO
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| InChi Key |
YKLKCCHLLFMWQE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H15N5O5/c1-6(18)20-3-7(2-17)21-5-16-4-13-8-9(16)14-11(12)15-10(8)19/h4,7,17H,2-3,5H2,1H3,(H3,12,14,15,19)
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| Chemical Name |
[2-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]-3-hydroxypropyl] acetate
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : 50 mg/mL (168.20 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.41 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 2: 2.5 mg/mL (8.41 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3639 mL | 16.8197 mL | 33.6395 mL | |
| 5 mM | 0.6728 mL | 3.3639 mL | 6.7279 mL | |
| 10 mM | 0.3364 mL | 1.6820 mL | 3.3639 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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