GCV

Ganciclovir
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Description

Chemical and Pharmacological Profile

Molecular formula: C₉H₁₃N₅O₄
Molecular weight: 255.23 g/mol
Mechanism of action:

  • Requires phosphorylation by viral UL97 kinase in CMV-infected cells

  • Triphosphate form incorporates into viral DNA, causing chain termination

  • Selective toxicity: 10-100× higher affinity for viral vs human DNA polymerases

Approved Uses:

  • CMV retinitis treatment in AIDS patients

  • CMV prophylaxis in organ transplant recipients

Off-label Applications:

  • Adjuvant therapy in suicide gene systems (HSV1-TK)

  • Experimental anticancer combinations

Mutagenicity and Carcinogenicity:

Study ParameterFindingsSource
Patient cohort22/121,771 showed GCV-associated mutations
Cancer typesLeukemia, colorectal, renal, and skin cancers
Co-factorsMycophenolate increases mutagenic potential 3.8×

Antiviral Combinations:

Combination PartnerEffectEC₅₀ Reduction
FoscarnetSynergistic38%
ArtemisininStrong synergy72%
SunitinibAntagonisticN/A
Data from in vitro models

Resistance Profiles:

UL97 MutationGCV EC₅₀ (μM)Fold Change
Wild-type1.6 ± 0.2
A594V9.2 ± 1.55.7×
A594S6.8 ± 2.04.2×
Clinical isolates analysis

Pharmacokinetics and Monitoring

  • Half-life: 2.5-4.2 hours (IV), prolonged in renal impairment

  • TDM thresholds:

    • Efficacy: Trough >0.5 μg/ml

    • Neurotoxicity risk: Peak >6.2 μg/ml

Emerging Therapeutic Strategies

Anticancer combinations:

  • With methotrexate: ↑ cellular accumulation 13-21×

  • Breast cancer models show 41-56% viability reduction

Novel delivery systems:

  • Intravitreal implants (Vitrasert®) sustain drug release >8 months

Product Specs

Introduction
Ganciclovir (GCV) is a pro-drug nucleoside analog that requires phosphorylation for activation. It is a valuable tool in cancer research, particularly in gene therapy studies. GCV is structurally similar to 2'-deoxy-guanosine and functions by being phosphorylated into a deoxyguanosine triphosphate (dGTP) analog. This analog competitively inhibits the incorporation of dGTP by viral DNA polymerase, effectively halting viral DNA elongation. When a viral suicide gene encoding thymidine kinase is expressed, it converts the non-toxic pro-drug GCV into its active phosphorylated form. This active form is then integrated into the DNA of replicating eukaryotic cells, leading to the death of the dividing malignant cell. This process results in irreversible cell cycle arrest at the G2-M checkpoint. The role of gap junctions in the bystander effect of ganciclovir has been a subject of investigation. Furthermore, GCV has been employed to study telomere loss and assess viral sensitivity to antiviral therapies. In molecular biology, GCV is utilized to select against random recombination events, particularly when homologous recombination of a specific gene is desired.
Description
Ganciclovir is a white to off-white crystalline powder. Its molecular formula is C9H13N5O4, and its molecular weight is 255.23.
Physical Appearance
White lyophilized (freeze-dried) powder that has been sterilized by filtration.
Solubility
To reconstitute the lyophilized Ganciclovir, it is recommended to dissolve it in sterile 18 megaohm-cm H2O at a concentration of at least 100 micrograms per milliliter. This solution can then be further diluted in other aqueous solutions as needed.
Stability
While lyophilized Ganciclovir remains stable at room temperature for up to 3 weeks, it is recommended to store it at 4 degrees Celsius for optimal long-term stability.
Purity
Greater than 99.0% pure.

Q&A

Academic research on Gross Calorific Value (GCV) addresses critical energy measurement challenges through rigorous methodologies. Below are structured FAQs reflecting scientific depth, prioritized by research complexity, with methodological guidance and empirical data from peer-reviewed studies.

Advanced Research: Predictive Modeling

Q: How do regression models for GCV prediction address coal quality variability across geological formations? Methodological Answer:

  • Data Preprocessing

    • Cluster samples by mining region and stratigraphic layer

    • Apply Box-Cox transformations for non-normal distributions

  • Model Development

    • Comparative analysis of ML algorithms:

      ModelMAE (kcal/kg)
      Random Forest1270.91
      XGBoost1190.93
      Linear Regression2980.72
    • Validate using temporal holdout (train on 2017–2020, test on 2021)

  • Policy Integration

    • Conduct error dispersion analysis (σ ≤ 150 kcal/kg for regulatory acceptance)

    • Implement Monte Carlo simulations for grade misclassification risks

Data Contradiction Analysis

Q: How to resolve discrepancies between laboratory GCV measurements and field observations in power plants? Methodological Approach:

  • Root Cause Analysis Framework:

    • Sample Integrity: Verify chain-of-custody protocols for rail-transported samples (41-day testing delays observed at NCL )

    • Measurement Conditions:

      FactorLab ControlField Variance
      Temperature23°C ± 1°C18–38°C seasonal
      Humidity45% RH30–85% RH
    • Statistical Reconciliation:

      • Apply Bland-Altman analysis for method comparison

      • Use Deming regression for non-constant error ratios

Experimental Optimization

Q: What calibration protocols minimize instrumental drift in long-term GCV studies? Stepwise Methodology:

  • Primary Standardization:

    • Benzoic acid (certified ΔcU = 26,434 J/g) daily validation

  • Drift Mitigation:

    • Thermistor recalibration every 200 samples

    • Oxygen purity verification (≥99.995% pO₂)

  • Quality Control:

    • Include NIST SRM® 1592c (Subbituminous Coal) in every 50-sample batch

Advanced Policy-Research Integration

Q: How does error distribution analysis inform regulatory acceptance of empirical GCV formulas? Technical Process:

  • Calculate regulatory risk thresholds:

    Error BandGrade Misclassification Probability
    ±150 kcal/kg8.7%
    ±200 kcal/kg14.2%
  • Conduct policy simulations using agent-based modeling for stakeholder acceptance

Product Science Overview

Introduction

Ganciclovir is an antiviral medication primarily used to treat cytomegalovirus (CMV) infections. It is particularly effective in immunocompromised individuals, such as those with AIDS or those who have undergone organ transplants . Ganciclovir is marketed under various brand names, including Cytovene, Cymevene, and Vitrasert .

History and Development

Ganciclovir was patented in 1980 and approved for medical use in 1988 . It was developed as a potent inhibitor of herpesvirus DNA replication, making it a valuable tool in the treatment of CMV infections . The drug’s development was driven by the need for effective antiviral therapies for immunocompromised patients who are particularly vulnerable to CMV infections.

Chemical Structure and Properties

Ganciclovir is a synthetic analog of 2’-deoxy-guanosine, a component of DNA. Its chemical formula is C9H13N5O4, and it has a molar mass of 255.234 g/mol . The drug is metabolized to its active triphosphate form by cellular enzymes, which then inhibits viral DNA polymerase more effectively than cellular polymerase .

Mechanism of Action

Ganciclovir’s antiviral activity is highly selective. It requires conversion to its active form by a virus-encoded enzyme, thymidine kinase (TK), which is present in CMV-infected cells . Once activated, ganciclovir triphosphate inhibits viral DNA polymerase, preventing the replication of viral DNA and thereby controlling the infection .

Preparation Methods

Ganciclovir is available in various forms, including intravenous (IV) infusion, oral capsules, and intravitreal implants . The IV form is typically used for severe infections and is prepared by reconstituting a dry powder equivalent to 500 mg of ganciclovir in a sterile environment . The reconstituted solution is then administered via a volumetric pump over one hour to minimize venous irritation .

Clinical Uses

Ganciclovir is indicated for the treatment of:

  • CMV retinitis in severely immunocompromised individuals
  • CMV pneumonitis in bone marrow transplant recipients
  • Prevention of CMV disease in bone marrow and solid organ transplant recipients
  • Acute CMV colitis in HIV/AIDS patients

It has also been used with some success in treating Human herpesvirus 6 infections and herpes simplex virus epithelial keratitis .

Adverse Effects

Ganciclovir is associated with a range of serious hematological adverse effects, including granulocytopenia, neutropenia, anemia, and thrombocytopenia . Other common side effects include fever, nausea, vomiting, diarrhea, abdominal pain, and increased liver enzymes . Due to its potential carcinogenic, teratogenic, and mutagenic effects, ganciclovir is handled as a cytotoxic drug in clinical settings .

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