| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
HIV-1;HIV-2
Tenofovir exalidex targets the HIV-1 reverse transcriptase. As a nucleotide analog prodrug, it is converted intracellularly to tenofovir and then phosphorylated to tenofovir diphosphate, which inhibits HIV-1 reverse transcriptase by competing with the natural substrate deoxyadenosine triphosphate and causing chain termination. The exalidex prodrug moiety enhances oral absorption and lymphatic delivery to lymphoid tissues. |
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| ln Vitro |
Tenofovir exalidex exhibits a consistent >300-fold increase in activity compared to Tenofovir against various viruses across multiple cell systems. Tenofovir exalidex is effective against MNR mutants, including those that don't react to any of the NRTIs that are on the market right now. CMX157's average EC50 in PBMCs was 2.6 nM (range, 0.2 to 7.2 nM) against a panel of 27 wild-type HIV-1 isolates representing group M subtypes A to G and group O. This is noteworthy[1].
Although cyclophilins are not known to bind to HBV polymerase or participate in DNA elongation, tenofovir exalidex works as a therapeutic by blocking HBV polymerase-mediated HBV DNA elongation. Tenofovir exalidex (direct-acting) and CRV431 (host-targeting) together have a combination effect on HBV DNA production that is more consistent with the two drugs acting on different stages of the HBV life cycle[3]. In vitro, tenofovir exalidex is a potent inhibitor of HIV-1 replication. Its activity is assessed using HIV-1-infected cell lines. The compound shows enhanced potency and cellular uptake compared to tenofovir disoproxil fumarate due to the lipid ester prodrug design. Its selectivity for viral reverse transcriptase over host DNA polymerases contributes to its safety profile. |
| ln Vivo |
Oral administration of tenofovir exalidex (Sprague-Dawley rats) at doses of 10, 30, or 100 mg/kg/day to rats for seven days does not appear to be toxic[2]. Metovir exalidex (5–10 mg/kg; oral gavage; once daily for 16 days) reduces HBV DNA levels in the liver in a dose-dependent manner[3].
In vivo, tenofovir exalidex has been studied for the treatment of HIV-1 infection. The compound's prodrug design improves oral bioavailability and delivers higher intracellular concentrations of the active metabolite in target cells, particularly in lymphoid tissues. This may provide improved efficacy and a more favorable safety profile compared to other tenofovir formulations. |
| Enzyme Assay |
In vitro enzyme assays for tenofovir exalidex measure its inhibition of HIV-1 reverse transcriptase. The enzyme is incubated with its template/primer, nucleotides, and varying concentrations of the compound. DNA synthesis is measured by incorporation of radiolabeled nucleotides. IC50 values are calculated from dose-response curves. The compound's mechanism as a chain terminator is confirmed by its effects on DNA elongation.
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| Cell Assay |
CMX157 is a lipid (1-0-hexadecyloxypropyl) conjugate of the acyclic nucleotide analog tenofovir (TFV) with activity against both wild-type and antiretroviral drug-resistant HIV strains, including multidrug nucleoside/nucleotide analog-resistant viruses. CMX157 was consistently >300-fold more active than tenofovir against multiple viruses in several different cell systems. CMX157 was active against all major subtypes of HIV-1 and HIV-2 in fresh human peripheral blood mononuclear cells (PBMCs) and against all HIV-1 strains evaluated in monocyte-derived macrophages, with 50% effective concentrations (EC(50)s) ranging between 0.20 and 7.2 nM. The lower CMX157 EC(50)s can be attributed to better cellular uptake of CMX157, resulting in higher intracellular levels of the active antiviral anabolite, TFV-diphosphate (TFV-PP), inside target cells. CMX157 produced >30-fold higher levels of TFV-PP in human PBMCs exposed to physiologically relevant concentrations of the compounds than did TFV. Unlike conventional prodrugs, including TFV disoproxil fumarate (Viread), CMX157 remains intact in plasma, facilitating uptake by target cells and decreasing relative systemic exposure to TFV. There was no detectable antagonism with CMX157 in combination with any marketed antiretroviral drug, and it possessed an excellent in vitro cytotoxicity profile. CMX157 is a promising clinical candidate to treat wild-type and antiretroviral drug-resistant HIV, including strains that fail to respond to all currently available nucleoside/nucleotide reverse transcriptase inhibitors[1].
In vitro cell-based assays for tenofovir exalidex use HIV-1-infected cell lines. Cells are treated with serial dilutions of the compound, and viral replication is measured by quantifying viral RNA or antigen production. The EC50 for inhibition of viral replication is determined from dose-response curves. Cytotoxicity is assessed in parallel using uninfected cells. Cellular uptake and intracellular conversion to the active metabolite are also measured. |
| Animal Protocol |
Animal Model: transgenic mice that are female Tg05 transgenic mice for HBV (C57BL/6)[1]
Dosage: 5 mg/kg, 10 mg/kg Administration: Oral gavage; daily for a period of 16 days Result: For low-dose (5 mg/kg/day) and high-dose (10 mg/kg/day), the reductions in HBV DNA were 55% and 97%, respectively. In vivo animal models for tenofovir exalidex include mouse models of HIV-1 infection. The compound is administered orally, and its effects on viral load and tissue distribution are evaluated. Pharmacokinetic studies measure drug exposure in plasma and lymphoid tissues. The compound's enhanced delivery to lymphoid tissues is a key feature of the prodrug design. |
| ADME/Pharmacokinetics |
Tenofovir exalidex has a molecular formula of C24H38N5O5P and a molecular weight of 507.56. It is also known as CMX-157. The compound is a lipid ester prodrug of tenofovir designed to improve oral bioavailability and deliver higher intracellular concentrations in target cells. It is administered orally. Pharmacokinetic parameters are documented in research publications.
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| Toxicity/Toxicokinetics |
The toxicity profile of tenofovir exalidex is characterized in preclinical and clinical studies. Common adverse effects may include gastrointestinal discomfort and headache. Renal toxicity is expected to be reduced compared to tenofovir disoproxil fumarate due to lower systemic tenofovir exposure. The compound is for research use only and not for human use.
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| References |
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| Additional Infomation |
Tenofovir alafenamide is being studied in the clinical trial NCT01080820 (a study of the safety, tolerability and pharmacokinetics of a single dose of CMX157 in healthy volunteers).
Tenofovir exalidex is a prodrug of tenofovir used for the treatment of HIV-1 infection. It is also known as CMX-157. The compound is a lipid ester prodrug designed to improve oral bioavailability and deliver higher intracellular concentrations of the active metabolite in target cells, particularly in lymphoid tissues. Tenofovir exalidex is used for research purposes only. |
| Molecular Formula |
C28H52N5O5P
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|---|---|
| Molecular Weight |
569.7278
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| Exact Mass |
569.371
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| Elemental Analysis |
C, 59.03; H, 9.20; N, 12.29; O, 14.04; P, 5.44
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| CAS # |
911208-73-6
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| Related CAS # |
202138-50-9n(fumarate);206184-49-8 (hydrate);379270-37-8n(alafenamide);206184-49-8 (hydrate);1571075-19-8n(aspartate);201341-05-1 Tenofovir dsoproxil);1236287-04-9 (Tenofovirnmaleate);1392275-56-7 (Tenofovir alafenamide hemifumarate);379270-38-9n(Tenofovir alafenamide fumarate);1453166-76-1 (Tenofovir disoproxil phosphate);1637632-97-3n(Tenofovir disoproxil succinate)
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| PubChem CID |
23628250
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| Appearance |
White to off-white solid powder.
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| LogP |
7.442
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
25
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| Heavy Atom Count |
39
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| Complexity |
650
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C(N1C=NC2C(=NC=NC1=2)N)[C@@H](C)OCP(O)(=O)OCCCOCCCCCCCCCCCCCCCC
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| InChi Key |
BPPMYUZIZUESBY-MLEONAHRSA-N
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| InChi Code |
InChI=1S/C28H52N5O5P/c1-3-4-5-6-7-8-9-10-11-12-13-14-15-16-18-36-19-17-20-38-39(34,35)24-37-25(2)21-33-23-32-26-27(29)30-22-31-28(26)33/h22-23,25H,3-21,24H2,1-2H3,(H,34,35)(H2,29,30,31)/t25-/m1/s1
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| Chemical Name |
3-(hexadecyloxy)propyl hydrogen ((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonate
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| Synonyms |
Tenofovir exalidex; HDP-Tenofovir; Tenofovir; CMX-157; HDP-Tenofovir; CMX-157; 3-(Hexadecyloxy)propyl hydrogen ((((R)-1-(6-amino-9H-purin-9-yl)propan-2-yl)oxy)methyl)phosphonate; K7J545MEMA; 9-R-(2-(Phosphonomethoxy)propyl)adenine; CMX157; CMX 157
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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 : ~100 mg/mL (~175.52 mM）
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2 mg/mL (3.51 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.0 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 | 1.7552 mL | 8.7761 mL | 17.5522 mL | |
| 5 mM | 0.3510 mL | 1.7552 mL | 3.5104 mL | |
| 10 mM | 0.1755 mL | 0.8776 mL | 1.7552 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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