| Size | Price | Stock | Qty |
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| Other Sizes |
Purity: ≥98%
| Targets |
Reverse transcriptase (IC50 = 0.3 µM); NNRTI
The primary target of Loviride is the reverse transcriptase (RT) enzyme of HIV-1. As a non-nucleoside reverse transcriptase inhibitor (NNRTI), it binds to an allosteric site on the enzyme, distinct from the active site where nucleoside analogs bind. This binding induces a conformational change in the enzyme that inhibits its polymerase activity, thereby blocking the conversion of viral RNA into DNA, a critical step in the HIV life cycle. Loviride inhibits HIV-1 reverse transcriptase with an IC50 of 0.3 µM. It also shows activity against HIV-2 and SIV reverse transcriptase. |
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| ln Vitro |
In MT-4 cells, loviride (0.01 µM) suppresses HIV-1(IIIB) replication as well as HIV-2 and SIV. The EC50 for HIV-2 (ROD), HIV-2 (EHO), and HIV-2 (ROD) is 85.5 µM and 7.4 µM, respectively. SIV (mndGB1), SIV (mac251), and SIV (agm3) are, in that order, 11.4, 28.5, and 57.0 µM [1].
Loviride demonstrates potent in vitro anti-HIV activity. It inhibits HIV-1, HIV-2, and SIV replication in MT-4 cells. The compound's antiviral activity is mediated through the inhibition of viral reverse transcriptase. In addition to its antiviral effects, Loviride has been evaluated for its cytotoxic concentration (CC50) in MT-4 cells, which is 137 μM. The compound's selectivity index (ratio of CC50 to EC50) indicates a favorable therapeutic window in vitro. However, detailed IC50 values for different HIV strains are not extensively reported. |
| ln Vivo |
In vivo data for Loviride are limited in the available literature. The compound was investigated in clinical trials as a potential treatment for HIV infection but was not ultimately approved. These clinical studies would have evaluated its antiviral efficacy, safety, and pharmacokinetics in HIV-infected patients. However, the specific results of these clinical trials, including dosing regimens, efficacy endpoints, and adverse event profiles, are not detailed in the available literature. The compound is now primarily used as a research tool.
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| Enzyme Assay |
Objective: To investigate whether, in addition to HIV-1, different strains of HIV-2 (ROD and EHO) and SIV (mac251, agm3 and mndGB1) are sensitive to a selection of NNRTI i.e. delavirdine, the HEPT derivative I-EBU (MKC-442), 8-chloro-TIBO (tivirapine), alpha-APA (Loviride), nevirapine and the pyridinone derivative L-697,661.
Methods and results: The NNRTI tested inhibited the replication of the different strains of HIV-2 and SIV at micromolar concentrations. The inhibitory effects of the NNRTI on HIV-2-induced cytopathicity correlated well with their inhibitory effects on HIV-2 RT activity. Drug-resistant HIV-2 (EHO) variants containing the Ser102Leu and/or Glu219Asp mutations in their RT were selected after passaging the virus in MT-4 cells in the presence of increasing concentrations of delavirdine. The EHO virus mutants were at least 20-fold less susceptible to the antiviral effects of delavirdine. Some cross-resistance, depending on the mutant strain, was observed with the other NNRTI tested (i.e. MKC-442, tivirapine, Loviride and pyridinone L-697,661). Conclusions: Our data demonstrate that NNRTI are not exclusively specific for HIV-1 but are also inhibitory to different HIV-2 and SIV strains. These observations will have important implications for the development of new NNRTI with higher activity against both HIV-1 and HIV-2. Furthermore, in view of their anti-SIV activity, NNRTI could be evaluated further for their in vivo anti-retrovirus efficacy in non-human primate models [1]. In vitro enzyme assays for Loviride typically involve measuring its inhibition of HIV-1 reverse transcriptase activity. Recombinant HIV-1 reverse transcriptase enzyme is incubated with a template-primer and nucleotide substrates in the presence of varying concentrations of the compound. The incorporation of radiolabeled nucleotides into the growing DNA strand is measured to determine the enzyme activity. The IC50 for inhibition is calculated from the dose-response curve, with Loviride showing an IC50 of 0.3 µM. |
| Cell Assay |
Cellular assays for Loviride are performed in HIV-susceptible cell lines, such as MT-4 cells. Cells are infected with HIV-1, HIV-2, or SIV and treated with various concentrations of the compound. After several days of culture, viral replication is measured by quantifying viral antigens (e.g., p24 for HIV-1) in the culture supernatant or by assessing the cytopathic effect of the virus on the cells. The compound's antiviral activity is expressed as the EC50 (effective concentration for 50% inhibition of viral replication). Cytotoxicity is assessed in parallel in uninfected cells to determine the CC50.
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| Animal Protocol |
In vivo animal studies with Loviride are not extensively documented in the available literature. As an NNRTI developed for HIV treatment, the compound would have been evaluated in animal models of HIV infection, such as humanized mouse models or non-human primate models infected with simian immunodeficiency virus (SIV). These studies would assess the compound's antiviral efficacy, pharmacokinetics, and safety in vivo. However, specific protocols and results are not detailed in the available sources.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for Loviride are not extensively reported in the available literature. As a compound that was investigated in clinical trials, it would have been characterized for its absorption, distribution, metabolism, and excretion (ADME) properties. However, specific pharmacokinetic parameters such as half-life, bioavailability, protein binding, and route of elimination are not detailed in the available literature. The compound is typically dissolved in DMSO for in vitro studies.
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| Toxicity/Toxicokinetics |
Toxicological data for Loviride are limited in the available literature. The compound's cytotoxic concentration (CC50) in MT-4 cells is 137 μM, indicating a relatively low cytotoxicity in this cell line. As a compound that was investigated in clinical trials, it would have undergone extensive toxicological evaluation, including acute and chronic toxicity studies, genotoxicity, and carcinogenicity assessments. However, specific toxicological data are not detailed in the available literature.
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| References | |
| Additional Infomation |
Loveride is an organic molecular entity.
Following the initial discovery of 1-(2-hydroxyethoxymethyl)-6-(phenylthio)thymine (HEPT) and tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepine-2(1H)-one and thionone (TIBO) derivatives, several other non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) have been discovered, including nevirapine (BI-RG-587), pyridone derivatives (L-696,229 and L-697,661), deraviridine (U-90152), α-aniline phenylacetamide (α-APA), and various other types of NNRTIs. A hallmark of NNRTIs is their ability to interact with specific sites (“pockets”) of the HIV-1 RT. [1] Loviride is a research-grade compound that was previously investigated as a potential HIV therapeutic but was not approved for clinical use. Its primary application is as a pharmacological tool for studying HIV reverse transcriptase and for screening potential NNRTI drug candidates. The compound's mechanism of action as an allosteric inhibitor of reverse transcriptase makes it a valuable reference standard in antiviral drug discovery. It is also used to study resistance mechanisms to NNRTIs. |
| Molecular Formula |
C17H16CL2N2O2
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|---|---|
| Molecular Weight |
351.22714
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| Exact Mass |
350.059
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| Elemental Analysis |
C, 58.14; H, 4.59; Cl, 20.19; N, 7.98; O, 9.11
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| CAS # |
147362-57-0
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| PubChem CID |
3963
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.354g/cm3
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| Boiling Point |
550.3ºC at 760mmHg
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| Melting Point |
226.3 °C
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| Flash Point |
286.6ºC
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| Vapour Pressure |
3.69E-12mmHg at 25°C
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| Index of Refraction |
1.637
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| LogP |
5.365
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
23
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| Complexity |
436
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
CJPLEFFCVDQQFZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H16Cl2N2O2/c1-9-6-7-11(10(2)22)14(8-9)21-16(17(20)23)15-12(18)4-3-5-13(15)19/h3-8,16,21H,1-2H3,(H2,20,23)
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| Chemical Name |
2-((2-acetyl-5-methylphenyl)amino)-2-(2,6-dichlorophenyl)acetamide
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| Synonyms |
R-89439; R 89439; R89439; loviride; 147362-57-0; 2-(2-acetyl-5-methylanilino)-2-(2,6-dichlorophenyl)acetamide; CHEMBL37624; 3S1R1LZ09H; 2-((2-acetyl-5-methylphenyl)amino)-2-(2,6-dichlorophenyl)acetamide; R 089439; R089439.
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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 : ~62.5 mg/mL (~177.95 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (17.79 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 62.5 mg/mL clear DMSO stock solution to 900 μL 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 | 2.8471 mL | 14.2357 mL | 28.4714 mL | |
| 5 mM | 0.5694 mL | 2.8471 mL | 5.6943 mL | |
| 10 mM | 0.2847 mL | 1.4236 mL | 2.8471 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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