| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
The primary target of rel-Carbovir monophosphate is HIV reverse transcriptase (RT). As the monophosphate form, it requires further phosphorylation by cellular kinases to the active triphosphate form. The carbovir triphosphate competes with natural deoxyguanosine triphosphate (dGTP) for incorporation into the growing viral DNA chain by reverse transcriptase. Once incorporated, it acts as a chain terminator because it lacks the 3'-hydroxyl group necessary for further DNA elongation, thereby blocking HIV replication.
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| ln Vitro |
In vitro, rel-Carbovir monophosphate acts as an inhibitor of HIV replication by specifically blocking the incorporation of nucleic acid precursors into DNA. As the monophosphate derivative, it is the active anabolite that is further phosphorylated intracellularly to the active triphosphate. Carbovir triphosphate has potent anti-HIV-1 activity with an EC50 (half-maximal effective concentration) in the low nanomolar range (typically 10-100 nM) against laboratory strains in MT-4 cells or peripheral blood mononuclear cells. It has low cytotoxicity (CC50 >100 uM).
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| ln Vivo |
In vivo, the parent drug abacavir (which is converted to carbovir monophosphate) is an FDA-approved antiretroviral drug used in combination therapy for HIV-1 infection. Abacavir is orally bioavailable (about 83%) and is metabolized by alcohol dehydrogenase to the 5'-carboxylic acid, and via glucuronosyltransferase to the 5'-glucuronide. The active carbovir triphosphate has a long intracellular half-life (~12 hours) in lymphocytes. Abacavir has shown efficacy in reducing viral load and increasing CD4+ T-cell counts in HIV-infected patients.
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| Enzyme Assay |
A non-cellular assay for reverse transcriptase inhibition uses recombinant HIV-1 RT. The reaction mixture (50 uL) contains 50 mM Tris-HCl (pH 7.8), 5 mM MgCl2, 1 mM DTT, 50 uM dGTP, 50 uM dATP, 50 uM dTTP, 50 uM dCTP, 0.5 uM [3H]-dGTP, and 0.5 ug of template-primer (e.g., poly(rA)-oligo(dT)). The test compound (rel-Carbovir monophosphate) is pre-incubated with the enzyme for 10 min, then the reaction is initiated. After 30 min at 37degC, the acid-insoluble product is precipitated, filtered, and counted. The IC50 is determined.
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| Cell Assay |
Cell-based anti-HIV assays are performed in MT-4 cells or PBMC. Cells are infected with HIV-1 (e.g., IIIB strain) at an MOI of 0.01-0.1. After 1-2 h adsorption, the cells are washed and seeded in 96-well plates. rel-Carbovir monophosphate (0.01-100 uM) is added. After 5-7 days, HIV replication is quantified by p24 antigen ELISA or by syncytia formation. The EC50 is calculated. Cytotoxicity is measured in parallel using the MTT assay to calculate the CC50. The selectivity index (SI) is CC50/EC50.
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| Animal Protocol |
Abacavir (the parent prodrug) has been studied in animal models of HIV. In a SCID-hu mouse model, oral abacavir (40-120 mg/kg/day for 14 days) significantly reduced HIV-1 p24 antigen levels in the implanted human thymus/liver tissue by >90% compared to vehicle control. In the rat, abacavir has oral bioavailability of ~80% and a plasma half-life of 1-2 hours. For efficacy studies, the test compound (abacavir, not the monophosphate) is administered orally or intraperitoneally. The parent drug is used in vivo because the monophosphate is too polar to be absorbed.
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| ADME/Pharmacokinetics |
rel-Carbovir monophosphate (MW 327.23) is a polar phosphate ester. It is not orally bioavailable and is used as a research standard. The parent drug abacavir (which is the free base) has logP 1.2. Abacavir is rapidly absorbed (Tmax 1-2 h), with an oral bioavailability of ~83%. The plasma half-life of abacavir is 1.5 h, but the intracellular half-life of the active triphosphate (carbovir triphosphate) is ~12 h in lymphocytes. Metabolism occurs via alcohol dehydrogenase (to the 5'-carboxylic acid) and via glucuronosyltransferase (to the 5'-glucuronide). Excretion is renal (80% as metabolites).
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| Toxicity/Toxicokinetics |
Abacavir has a favorable safety profile but can cause hypersensitivity reactions (HSR) in genetically susceptible individuals (associated with HLA-B*5701 allele). Other side effects include nausea, headache, fatigue, and diarrhea. The monophosphate form is for research use only and is not a drug. Standard safety precautions for handling nucleoside analogs (gloves, lab coat, goggles, fume hood) should be followed. Not for human consumption.
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| References | |
| Additional Infomation |
rel-Carbovir monophosphate (CAS 144490-73-3) is the active anabolite of the anti-HIV drug abacavir (Ziagen®). It is used as a reference standard in pharmacokinetic studies to measure abacavir triphosphate levels in lymphocytes by LC-MS/MS. It is also a useful tool for studying the mechanism of action of NRTIs and for evaluating drug resistance mutations in HIV reverse transcriptase. The compound is for research use only, not for therapeutic application.
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| Molecular Formula |
C11H14N5O5P
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|---|---|
| Molecular Weight |
327.23
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| Exact Mass |
327.073
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| CAS # |
144490-73-3
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| PubChem CID |
135457337
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| Appearance |
Typically exists as solids at room temperature
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| LogP |
0.271
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
22
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| Complexity |
575
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OP(OC[C@@H]1C=C[C@H](N2C=NC3C(N=C(NC2=3)N)=O)C1)(O)=O
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| InChi Key |
OJDRNVIJFVCXOM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H14N5O5P/c12-11-14-9-8(10(17)15-11)13-5-16(9)7-2-1-6(3-7)4-21-22(18,19)20/h1-2,5-7H,3-4H2,(H2,18,19,20)(H3,12,14,15,17)
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| Chemical Name |
[4-(2-amino-6-oxo-1H-purin-9-yl)cyclopent-2-en-1-yl]methyl dihydrogen phosphate
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| Synonyms |
Abacavir monophosphate
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
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 Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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)] Oral Formulations
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 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0560 mL | 15.2798 mL | 30.5595 mL | |
| 5 mM | 0.6112 mL | 3.0560 mL | 6.1119 mL | |
| 10 mM | 0.3056 mL | 1.5280 mL | 3.0560 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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