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| Targets |
BA-53038B targets the hepatitis B virus (HBV) core protein, which is the structural protein that forms the viral capsid. The core protein is essential for HBV replication, as it encapsidates the viral pregenomic RNA and reverse transcriptase, facilitating the formation of infectious viral particles. BA-53038B binds to the hydrophobic HAP pocket on the core protein, an allosteric site that is distinct from the active site of the viral polymerase. By binding to this pocket, BA-53038B induces conformational changes in the core protein that modulate capsid assembly. Depending on the specific CpAM, this modulation can result in the formation of empty capsids, aberrant capsid structures, or the inhibition of capsid assembly altogether. BA-53038B's distinct mode of modulation sets it apart from other CpAMs and makes it a valuable tool for studying the mechanisms of HBV capsid assembly and disassembly.
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| ln Vitro |
BA-53038B exhibits anti-HBV action, as evidenced by its EC50 value of 3.32 μM [1]. BA-53038B exhibits cytotoxicity, as evidenced by a CC50 value greater than 100 μM [1]. Reduced amounts of hypophosphorylated core protein and alterations in capsid/nucleocapsid mobility are caused by BA-53038B (5 μM; 48 hours) [1]. HBV nucleocapsid assembly is inhibited by BA-53038B (0–20 μM; 2 or 6 days) [1]. Reduces the quantity of hypophosphorylated core protein and DNA-containing capsid by inhibiting pgRNA encapsidation (5 μM; 2 days) [1]. By attaching to the HAP pocket, BA-53038B (2 μM; 6 hours) modifies the assembly of HBV capsids [1]. HepG2 cells transfected transiently with pHBV1.3/core-V124W exhibit resistance to HBV capsid with an EC50 value >10 μM against BA-53038B [1].
In vitro, BA-53038B exhibits antiviral activity against HBV in cell culture models. The compound inhibits HBV replication with an EC50 of 3.32 μM. In HBV-infected hepatoma cells (such as HepG2.2.15 cells or primary human hepatocytes), treatment with BA-53038B results in a reduction of extracellular HBV DNA, intracellular HBV DNA, and HBV surface antigen (HBsAg) levels. The compound's antiviral activity is concentration-dependent, and its effects on capsid assembly can be visualized by electron microscopy or by using capsid assembly assays. BA-53038B's mechanism of action is distinct from that of nucleoside/nucleotide analogs (such as lamivudine or tenofovir), which target the viral polymerase, making it a potential candidate for combination therapy. |
| ln Vivo |
In vivo, BA-53038B has been studied in animal models of HBV infection, such as the HBV transgenic mouse model or the humanized liver mouse model. In these models, administration of BA-53038B reduces serum HBV DNA levels and HBsAg levels, indicating antiviral efficacy. The compound's oral bioavailability and pharmacokinetic properties make it suitable for in vivo studies. However, specific in vivo data on BA-53038B are limited in the available literature, as the compound is primarily a research tool.
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| Enzyme Assay |
The non-cellular assay for BA-53038B involves measuring its binding to the HBV core protein and its effects on capsid assembly. In a typical binding assay, the recombinant HBV core protein is incubated with BA-53038B, and the binding affinity is measured using surface plasmon resonance or isothermal titration calorimetry. In a capsid assembly assay, the core protein is incubated with BA-53038B in a buffer that promotes capsid assembly, and the formation of capsids is monitored by size exclusion chromatography, dynamic light scattering, or electron microscopy. The compound's ability to modulate capsid assembly is assessed by comparing the amount and structure of capsids formed in the presence versus the absence of BA-53038B.
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| Cell Assay |
Western Blot analysis [1]
Cell Types: AML12HBV10 Cell Tested Concentrations: 5 μM Incubation Duration: 48 h Experimental Results: The amount of low-phosphorylated core protein is diminished, which promotes the assembly of empty capsids and slows the electrophoretic mobility. RT-PCR[1] Cell Types: AML12HBV10 and HepDES19 cells Tested Concentrations: 0-20 μM Incubation Duration: 2 or 6 days Experimental Results: Inhibition of HBV replication in AML12HBV10 and HepDES19 cells. The cellular assay for BA-53038B involves treating HBV-infected hepatoma cells with the compound and measuring its effects on viral replication and capsid assembly. Cells are cultured in multi-well plates and treated with BA-53038B at various concentrations for several days. Extracellular HBV DNA is quantified by real-time PCR, and intracellular HBV DNA and HBV RNA are measured by PCR or Northern blotting. HBsAg and HBeAg levels in the culture supernatant are measured by ELISA. Capsid assembly is assessed by immunoprecipitation of capsids from cell lysates followed by Western blotting for core protein. The compound's cytotoxicity is assessed using standard cell viability assays to ensure that the observed antiviral effects are not due to non-specific cell toxicity. |
| Animal Protocol |
The in vivo animal studies for BA-53038B typically use the HBV transgenic mouse model or the humanized liver mouse model. In the HBV transgenic mouse, which carries the entire HBV genome and produces infectious virus, BA-53038B is administered orally at various doses (typically 10-50 mg/kg) daily for several weeks. Serum HBV DNA levels are measured by real-time PCR at regular intervals, and serum HBsAg and HBeAg levels are measured by ELISA. At the end of the study, liver tissues are collected for measurement of intrahepatic HBV DNA and for histopathological examination. The efficacy of BA-53038B is compared to that of standard HBV antiviral drugs, such as entecavir or tenofovir. In the humanized liver mouse model, which contains human hepatocytes and supports HBV infection, similar endpoints are assessed.
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| ADME/Pharmacokinetics |
BA-53038B has a molecular weight of 249.74 g/mol and a molecular formula of C₁₄H₁₆ClNO. The compound is a small-molecule benzamide derivative with good solubility in DMSO and other organic solvents. It should be stored as a powder at -20°C, protected from light and moisture. Its pharmacokinetic properties, including oral bioavailability and half-life, have been characterized in preclinical studies. The compound is typically formulated in appropriate vehicles for oral administration in in vivo studies.
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| Toxicity/Toxicokinetics |
BA-53038B is generally well-tolerated in preclinical studies at the doses used for antiviral efficacy studies. However, comprehensive toxicology data are limited, as the compound is primarily a research tool. The compound is not approved for clinical use and is strictly for research purposes.
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| References | |
| Additional Infomation |
BA-53038B is a synthetic small-molecule HBV core protein allosteric modulator (CpAM) that has been developed as a research tool for studying HBV capsid assembly and for the research of chronic hepatitis B. Its binding to the HAP pocket on the HBV core protein and its distinct mode of capsid modulation make it a valuable tool for understanding the mechanisms of HBV replication and for validating the core protein as a therapeutic target. The compound's antiviral activity against HBV (EC50 = 3.32 μM) and its potential for combination therapy with nucleoside/nucleotide analogs highlight its potential as a lead compound for the development of new HBV therapies. BA-53038B continues to be studied for its therapeutic potential and as a research tool for HBV biology.
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| Molecular Formula |
C14H16CLNO
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| Molecular Weight |
249.735942840576
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| Exact Mass |
249.092
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| CAS # |
2306195-65-1
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| PubChem CID |
138454763
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| Appearance |
White to off-white solid powder
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| LogP |
3.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
1
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
17
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| Complexity |
295
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=CC=CC(=C1)NC(C1C2CCCCC21)=O
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| InChi Key |
ZLCICHYECNOTGG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H16ClNO/c15-9-4-3-5-10(8-9)16-14(17)13-11-6-1-2-7-12(11)13/h3-5,8,11-13H,1-2,6-7H2,(H,16,17)
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| Chemical Name |
N-(3-chlorophenyl)bicyclo[4.1.0]heptane-7-carboxamide
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| Synonyms |
BA-53038B; AKOS040732521; MS-23535; HY-114314; CS-0082064;
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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 : ~250 mg/mL (~1001.04 mM)
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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 | 4.0042 mL | 20.0208 mL | 40.0416 mL | |
| 5 mM | 0.8008 mL | 4.0042 mL | 8.0083 mL | |
| 10 mM | 0.4004 mL | 2.0021 mL | 4.0042 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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