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| 1mg |
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| 10mg |
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| Targets |
The primary target of XZ426 is the HIV integrase enzyme. Specifically, it is an integrase strand transfer inhibitor (INSTI) that prevents the integration of viral DNA into the host cell genome by binding to the integrase active site and blocking the strand transfer step, an essential part of the viral replication cycle.
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| ln Vitro |
Integrase (IN) strand transfer inhibitors (INSTI), the newest class of antiretroviral medications, target integrasomes. We constructed the complex with bictegravir (BIC), the most widely used second-generation INSTI and the most clinically approved INSTI overall, in order to gain a better understanding of how INSTIs interact with HIV intasomes. Of these, XZ426 is a front-runner that has outperformed all produced and clinically utilized compounds in terms of efficacy against known drug-resistant variants[1].
In non-cellular biochemical assays, XZ426 is identified as a potent integrase strand transfer inhibitor. It has been compared to other INSTIs and has been shown to be a front-runner compound, demonstrating efficacy against known drug-resistant variants that have been challenging for some existing clinically utilized antiretroviral drugs. |
| ln Vivo |
In vivo data for XZ426 is not detailed in the provided reference sheet. However, as an INSTI, its in vivo activity is presumed to be the reduction of viral load in HIV infection models. Its activity against drug-resistant variants in vitro suggests a potential for high in vivo efficacy, but specific animal model data is not shown here.
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| Enzyme Assay |
In non-cellular assays, the activity of XZ426 is typically measured using a strand transfer assay. In this assay, a pre-assembled integrase-DNA complex (intasome) is incubated with varying concentrations of XZ426. Then, a target DNA substrate is added, and the amount of integrated product is measured via gel electrophoresis or a plate-based assay to determine the inhibitor's efficacy.
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| Cell Assay |
Standard cell-based protocols for evaluating INSTIs like XZ426 involve HIV-1 infection assays in T-cell lines (such as MT-4 or CEM-SS cells). Cells are infected with HIV-1 in the presence of varying concentrations of XZ426. After 4-7 days, viral replication is quantified by measuring the cytopathic effect (using a viability dye like MTS) or by measuring levels of the p24 viral capsid protein in the supernatant.
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| Animal Protocol |
No specific in vivo animal protocol for XZ426 is provided. For in vivo studies of other INSTIs, the compound is typically formulated in a suitable vehicle (e.g., 0.5% methylcellulose or a solution of PEG400 and Tween 80) and administered via oral gavage to mice or rats. Efficacy is determined by measuring viral load or p24 levels in the plasma.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for XZ426 is not included in the provided reference. For small-molecule INSTIs, common PK parameters assessed in preclinical species include oral bioavailability, half-life (t1/2), and maximum concentration (Cmax). These data are used to determine the appropriate dosing frequency and exposure levels needed for antiviral efficacy.
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| Toxicity/Toxicokinetics |
No detailed toxicological data is available for XZ426 in these documents. As a potent antiviral agent, safety assessments are critical. In preclinical development, such compounds are typically subjected to cytotoxicity assays in various cell lines, hERG channel testing for cardiac safety, and CYP450 inhibition assays to assess drug-drug interaction potential.
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| References | |
| Additional Infomation |
XZ426 is a notable compound in the field of antiretroviral drug discovery because it targets HIV intasomes. The development of INSTIs represents a major advance, as these drugs are active against strains resistant to other drug classes like reverse transcriptase or protease inhibitors. XZ426's reported high efficacy against drug-resistant variants highlights its potential as a new generation inhibitor.
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| Molecular Formula |
C22H24F2N4O4
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|---|---|
| Molecular Weight |
446.447172164917
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| Exact Mass |
446.176
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| CAS # |
1638504-52-5
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| PubChem CID |
117697172
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| Appearance |
White to yellow solid powder
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| LogP |
3
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
32
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| Complexity |
707
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1(O)C2C(=CC(CCCCCCO)=CN=2)C(N)=C(C(NCC2=CC=C(F)C=C2F)=O)C1=O
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| InChi Key |
YZHRHLDMVJVVOL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H24F2N4O4/c23-15-7-6-14(17(24)10-15)12-27-21(30)18-19(25)16-9-13(5-3-1-2-4-8-29)11-26-20(16)28(32)22(18)31/h6-7,9-11,29,32H,1-5,8,12,25H2,(H,27,30)
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| Chemical Name |
4-amino-N-[(2,4-difluorophenyl)methyl]-1-hydroxy-6-(6-hydroxyhexyl)-2-oxo-1,8-naphthyridine-3-carboxamide
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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 | 2.2399 mL | 11.1995 mL | 22.3989 mL | |
| 5 mM | 0.4480 mL | 2.2399 mL | 4.4798 mL | |
| 10 mM | 0.2240 mL | 1.1199 mL | 2.2399 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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