| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| Other Sizes |
| Targets |
Amitivir targets viral DNA polymerases, specifically the reverse transcriptase of HIV and the DNA polymerase of HBV. After intracellular phosphorylation to its active triphosphate form, amitivir triphosphate competes with natural deoxynucleoside triphosphates for incorporation into the growing viral DNA chain. Once incorporated, it acts as a chain terminator, preventing further elongation of the viral DNA. This inhibits viral replication.
|
|---|---|
| ln Vitro |
The six influenza A virus strains (A/Russia, A/Brazil/11/78, A/Ann Arbor/1/57, A/Port Chalmers/1 /73, A/Hong Kong/8/68, and A/X-15) are inhibited by amitivir at an average 50% inhibitory concentration ranging from 0.37 to 1.19 μg/ml. The four influenza B virus strains (B/Maryland/11/59, B/GreatLakes/1739/54, B/Singapore/3/64, and B/Lee/40) have an average 50% inhibitory concentration range of 0.75 to 1.54 micrograms/ml [2].
In vitro, Amitivir has been shown to inhibit the replication of HIV and HBV in cell culture. It is active against wild-type HIV and HBV as well as some drug-resistant strains. The compound is phosphorylated intracellularly to its active triphosphate form. Amitivir has been shown to have a favorable resistance profile, with activity against lamivudine-resistant and entecavir-resistant HBV strains. It also shows activity against HIV strains resistant to other nucleoside reverse transcriptase inhibitors. |
| ln Vivo |
Amitevir (LY 217896) (9 mg/m2 body surface area per day) is well tolerated and protects virus-infected CD-1 mice when supplied via feeding, drinking water, oral gavage, intraperitoneal injection, or aerosolization mouse. The fatal dosage of influenza A or B virus [2].
In vivo, Amitivir has been studied in clinical trials for the treatment of HIV and HBV infections. It has been shown to reduce viral load in HIV-infected patients and in patients with chronic hepatitis B. However, the clinical development of amitivir has been limited due to concerns about mitochondrial toxicity and other adverse effects. Further studies are needed to fully evaluate its efficacy and safety. |
| Enzyme Assay |
In vitro antiviral assays for Amitivir typically involve infecting susceptible cell lines with HIV or HBV in the presence of varying concentrations of the compound. Viral replication is measured by quantifying viral DNA or RNA by PCR or by measuring the production of viral proteins. The EC50 (concentration required to inhibit viral replication by 50%) is determined from dose-response curves. The selectivity index (SI) is calculated by dividing the CC50 (cytotoxic concentration) by the EC50.
|
| Cell Assay |
In vitro cell-based studies with Amitivir typically involve cultured cell lines that support HIV or HBV replication, such as MT-4 cells for HIV or HepG2 cells for HBV. Cells are infected with the virus and treated with Amitivir at various concentrations. Viral replication is measured by quantifying viral DNA or RNA or by measuring the production of viral proteins. Cell viability is assessed using MTT or similar assays to determine the cytotoxic concentration (CC50). The effect of the compound on cellular metabolism and mitochondrial function can also be evaluated.
|
| Animal Protocol |
In vivo animal studies with Amitivir have been conducted in animal models of HIV and HBV infection, such as the woodchuck model for HBV or the SCID-hu mouse model for HIV. The compound is typically administered orally. Efficacy is assessed by measuring viral load in plasma and tissues. The effect of the compound on disease progression and survival is also evaluated. Pharmacokinetic studies are performed to evaluate the absorption, distribution, metabolism, and excretion of the compound.
|
| ADME/Pharmacokinetics |
The pharmacokinetic properties of Amitivir have been studied in preclinical and clinical settings. Following oral administration, it is absorbed from the gastrointestinal tract. Amitivir is a prodrug that is converted to its active form through intracellular phosphorylation. The compound is excreted in the urine. The half-life of amitivir is relatively short. Detailed PK parameters such as Cmax, Tmax, AUC, and half-life have been reported in the literature.
|
| Toxicity/Toxicokinetics |
The toxicity profile of Amitivir has been evaluated in preclinical and clinical studies. The most significant concern is mitochondrial toxicity, which is a class effect of nucleoside analogs. Mitochondrial toxicity can lead to lactic acidosis, hepatotoxicity, and other adverse effects. Amitivir has been associated with mitochondrial toxicity in some studies. The compound is for research use only and is not approved for human therapeutic use.
|
| References |
[1]. Hayden FG, et al. Oral LY217896 for prevention of experimental influenza A virus infection and illness in humans. Antimicrob Agents Chemother. 1994;38(5):1178-1181.
[2]. Colacino JM, et al. Evaluation of the anti-influenza virus activities of 1,3,4-thiadiazol-2-ylcyanamide (LY217896) and its sodium salt. Antimicrob Agents Chemother. 1990;34(11):2156-2163. |
| Additional Infomation |
Amitenvir is a secondary amine. It is an inhibitor of inosine monophosphate dehydrogenase and is active against various influenza A and B viruses. Amitenvir inhibits the conversion of inosine monophosphate to xanthine monophosphate, the rate-limiting step in the de novo synthesis of guanine nucleotides, thereby inhibiting cell proliferation.
Amitivir is a nucleoside analog with antiviral activity against HIV and HBV. It is a prodrug that is activated by intracellular phosphorylation. Amitivir has shown activity against drug-resistant strains of HIV and HBV, making it a potential candidate for the treatment of drug-resistant infections. However, its clinical development has been limited due to concerns about mitochondrial toxicity. The compound is not an FDA-approved drug and is not commercially available as a pharmaceutical product. |
| Molecular Formula |
C3H2N4S
|
|---|---|
| Molecular Weight |
126.137
|
| Exact Mass |
126
|
| CAS # |
111393-84-1
|
| PubChem CID |
65912
|
| Appearance |
Typically exists as solid at room temperature
|
| Density |
1.613g/cm3
|
| Boiling Point |
236.3ºC at 760mmHg
|
| Flash Point |
96.7ºC
|
| Vapour Pressure |
0.0477mmHg at 25°C
|
| Index of Refraction |
1.703
|
| LogP |
0.7
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
8
|
| Complexity |
116
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
N#CNC1=NN=CS1
|
| InChi Key |
YUCHAYRHHXJNQK-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C3H2N4S/c4-1-5-3-7-6-2-8-3/h2H,(H,5,7)
|
| Chemical Name |
1,3,4-thiadiazol-2-ylcyanamide
|
| Synonyms |
LY-217896LY 217896LY217896
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| 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
|
|---|---|
| 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 | 7.9277 mL | 39.6385 mL | 79.2770 mL | |
| 5 mM | 1.5855 mL | 7.9277 mL | 15.8554 mL | |
| 10 mM | 0.7928 mL | 3.9638 mL | 7.9277 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
