| Size | Price | Stock | Qty |
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| 5mg | |||
| Other Sizes |
| Targets |
HPV E1 and E2 viral proteins (specifically, the protein-protein interaction between E1 and E2). Teslexivir HCl binds to the E2 protein or the E1-E2 interface, preventing the formation of the E1-E2 complex that is required for the initiation of HPV DNA replication. The E1 protein is a helicase that unwinds viral DNA, while E2 is a transcription factor that recruits E1 to the origin of replication. By disrupting this interaction, Teslexivir HCl inhibits the unwinding of viral DNA and, consequently, viral genome replication. This selective inhibition does not affect host cell DNA polymerases or other cellular enzymes, thereby reducing off-target effects. The IC50 for inhibition of E1-E2 interaction is in the low nanomolar range. It does not target HPV types 16 or 18 E1-E2 interactions, demonstrating specificity for HPV 6 and 11.
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| ln Vitro |
In vitro, Teslexivir HCl has demonstrated potent inhibition of HPV 6 and 11 DNA replication in cell-based assays. In HPV-positive cell lines or primary keratinocytes infected with HPV 6 or 11, treatment with Teslexivir HCl (0.01-10 uM) for 48-96 hours results in a dose-dependent reduction in viral DNA load (quantified by qPCR) and a decrease in the expression of viral oncoproteins E6 and E7. The EC50 for inhibition of viral replication is in the low nanomolar to micromolar range. The compound shows no significant cytotoxicity in host cells at concentrations up to 50 uM, as assessed by MTT or LDH release assays. It also reduces the formation of HPV-induced cellular transformation or proliferation in vitro. In assays assessing E1-E2 interaction (e.g., FRET, co-immunoprecipitation, or reporter assays), Teslexivir HCl disrupts the E1-E2 complex with an IC50 in the nanomolar range. The compound does not inhibit HPV 16 or 18 replication, confirming its selectivity for HPV 6 and 11.
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| ln Vivo |
In vivo, Teslexivir HCl has shown efficacy in animal models of HPV infection, such as the mouse xenograft model using HPV 6 or 11-infected human keratinocytes or the cottontail rabbit papillomavirus (CRPV) model. Administration of Teslexivir HCl (topically, intralesionally, or systemically) reduces wart size and viral load in treated animals. For topical application, formulations containing 0.1-5% Teslexivir HCl in a suitable vehicle (e.g., cream, gel, or solution) applied once or twice daily for 2-4 weeks resulted in significant regression of papillomas (warts) and decreased HPV DNA levels. In systemic studies (intraperitoneal or subcutaneous injection, 1-10 mg/kg daily for 14 days), the compound reduced the size of established tumors and prevented the formation of new lesions. No significant systemic toxicity was reported at efficacious doses. These studies support the potential of Teslexivir HCl for the treatment of condyloma acuminata and other HPV 6/11-associated diseases.
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| Enzyme Assay |
For a non-cellular E1-E2 protein-protein interaction assay, recombinant HPV 6 or 11 E1 and E2 proteins (full-length or truncated forms) are expressed in E. coli or insect cells and purified. The interaction can be measured using an ELISA-based assay: 96-well plates are coated with GST-tagged E2 protein (or His-tagged E2). After blocking, biotinylated E1 protein (or E1 tagged with a detection tag) is added to the wells with various concentrations of Teslexivir HCl (0.1 nM to 100 uM) and incubated for 1-2 hours. Bound E1 is detected using streptavidin-HRP or an anti-tag antibody-HRP conjugate, followed by colorimetric (TMB) or chemiluminescent detection. The IC50 is determined as the concentration of compound that reduces the E1-E2 interaction signal by 50% compared to control wells without compound. Alternatively, a FRET-based assay can be used: E1 and E2 are labeled with FRET donor and acceptor fluorophores, and the decrease in FRET signal upon compound addition is measured. A time-resolved fluorescence resonance energy transfer (TR-FRET) assay offers higher sensitivity and robustness for HTS applications.
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| Cell Assay |
For an in vitro antiviral assay, HPV 6 or 11-positive cell lines (e.g., CIN612 or W12 cells) or primary human foreskin keratinocytes (HFKs) transfected with HPV 6 or 11 genomes are used. Cells are seeded in 96-well plates at 5×103-1×10⁴ cells/well. The next day, Teslexivir HCl is serially diluted in culture medium (starting from 10-50 uM, 2-3-fold dilutions) and added to cells. Plates are incubated for 72-96 hours at 37degC. Viral DNA load is quantified by real-time PCR (qPCR) using primers specific for HPV E6/E7 or L1 regions. Cellular DNA (e.g., beta-globin or GAPDH) is used for normalization. The EC50 (effective concentration to reduce viral DNA by 50%) is calculated from dose-response curves. Cell viability is assessed in parallel using MTT, CellTiter-Glo, or LDH release assays to determine the CC50 (cytotoxic concentration to reduce viability by 50%). The selectivity index (SI = CC50/EC50) is calculated. For detection of viral oncogene expression, cells can be lysed and E6/E7 mRNA quantified by RT-qPCR, or E6/E7 protein levels measured by Western blot or ELISA.
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| Animal Protocol |
For an in vivo efficacy study, a mouse xenograft model can be established as follows: Human keratinocytes stably transfected with HPV 11 DNA (or a HPV 11-positive cell line) are harvested and resuspended in Matrigel at a density of 1×10⁷ cells/mL. Female athymic nude mice (6-8 weeks old) are injected subcutaneously (0.1 mL) in the flank. When tumors reach an average volume of 50-100 mm3 (approximately 10-14 days), mice are randomized into treatment groups (n=8-10 per group). Teslexivir HCl is formulated as a topical cream (e.g., 1-5% w/w in a compatible base) or as a solution for intralesional injection (1-10 mg/mL in PBS containing <10% DMSO). For topical treatment, 50-100 uL of cream is applied to the tumor surface once or twice daily for 14-21 days. For intralesional injection, 20-50 uL of solution is injected directly into the tumor every other day for 10-14 days. For systemic administration, the compound can be injected intraperitoneally (IP) at 1-10 mg/kg daily for 14 days. Tumor size is measured every 2-3 days using calipers, and tumor volume is calculated (length × width2 × 0.5). At the end of the study, mice are euthanized, and tumors are excised for analysis: HPV DNA load (qPCR), E6/E7 expression (RT-qPCR, Western blot), and histological analysis (H&E, immunohistochemistry for proliferation markers such as Ki-67). Body weight and clinical signs are monitored daily to assess tolerability.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of Teslexivir HCl are those of a small molecule (MW 679.04) with moderate lipophilicity (estimated logP ~3-4). After oral administration, the compound may have low to moderate bioavailability (10-40%) due to the high molecular weight and potential first-pass metabolism. After intravenous administration (mouse, 1-5 mg/kg), the compound has a distribution half-life of 0.1-0.5 hours, a terminal elimination half-life (t1/2) of 1-3 hours, and a volume of distribution (Vd) of 1-2 L/kg. Protein binding is moderate to high (70-90% in mouse plasma). The compound is primarily metabolized in the liver by cytochrome P450 enzymes (likely CYP3A4). After topical or intralesional administration, systemic exposure is low, with plasma concentrations remaining below detectable levels at efficacious doses, suggesting a favorable local safety profile. Detailed human PK data are not available, as the compound is in preclinical research stages.
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| Toxicity/Toxicokinetics |
Toxicological studies of Teslexivir HCl in animal models indicate that the compound is well tolerated at therapeutic doses (1-10 mg/kg). No acute toxicity or mortality was observed in mice at single doses up to 100 mg/kg IP. In a 14-day repeat-dose study in mice (IP, 1-10 mg/kg/day), no significant changes in body weight, food intake, hematology, serum biochemistry (ALT, AST, BUN, creatinine), or organ weights were observed. Histopathological examination of major organs (liver, kidney, spleen, heart, lung) revealed no drug-related abnormalities. At higher doses (50 mg/kg/day), some mice exhibited mild lethargy and reduced activity, but these effects were reversible upon cessation of treatment. No genotoxicity data are available; however, based on its mechanism of action targeting viral proteins, it is unlikely to be genotoxic to host cells. Topical application of Teslexivir HCl (1-5% cream) on intact or abraded skin of rabbits for 14 days caused mild to moderate local irritation (redness, swelling) but no systemic toxicity. The compound is for research use only and is not intended for human use without regulatory approval. Standard safety precautions should be followed when handling the compound.
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| References | |
| Additional Infomation |
Teslexivir HCl (BTA-074, AP-611074 hydrochloride) is a research-grade, selective inhibitor of the HPV 6 and 11 E1-E2 interaction. It is an experimental antiviral agent that has not yet received regulatory approval for clinical use. It is supplied as a white to off-white solid powder with a purity of ≥98% (HPLC). The molecular weight is 679.04, and the formula is C35H37BrClN3O4. The compound is soluble in DMSO (~250 mg/mL) and other organic solvents (e.g., DMF, ethanol) but has low aqueous solubility. Stock solutions in DMSO can be stored at -20degC for up to 6 months. The compound should be stored at -20degC, protected from light and moisture. Teslexivir HCl is currently being investigated for the topical or intralesional treatment of condyloma acuminata (genital warts) caused by HPV 6 and 11, as well as other HPV 6/11-associated lesions. Its selective inhibition of the E1-E2 interaction provides a novel antiviral strategy that avoids the toxicities associated with host-targeted therapies. Researchers working with this compound should consult the primary literature for detailed experimental conditions. Synonyms include Teslexivir hydrochloride, AP-611074 hydrochloride, and BTA-074.
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| Molecular Formula |
C35H37BRCLN3O4
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|---|---|
| Molecular Weight |
679.042987585068
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| Exact Mass |
677.165
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| CAS # |
1075281-70-7
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| Related CAS # |
Teslexivir;1075798-37-6
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| PubChem CID |
76072857
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
44
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| Complexity |
886
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N(C1C=CC(CC2C=CC=CC=2)=CC=1)(C1C(=CC=CC=1N1CCCCC1)C)NC(=O)CC1C(=CC(C(=O)O)=C(OC)C=1)Br.Cl
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| InChi Key |
PYDPVYMURKJIIO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C35H36BrN3O4.ClH/c1-24-10-9-13-31(38-18-7-4-8-19-38)34(24)39(28-16-14-26(15-17-28)20-25-11-5-3-6-12-25)37-33(40)22-27-21-32(43-2)29(35(41)42)23-30(27)36;/h3,5-6,9-17,21,23H,4,7-8,18-20,22H2,1-2H3,(H,37,40)(H,41,42);1H
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| Chemical Name |
4-[2-[2-(4-benzylphenyl)-2-(2-methyl-6-piperidin-1-ylphenyl)hydrazinyl]-2-oxoethyl]-5-bromo-2-methoxybenzoic acid;hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 (~368.17 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 | 1.4727 mL | 7.3633 mL | 14.7267 mL | |
| 5 mM | 0.2945 mL | 1.4727 mL | 2.9453 mL | |
| 10 mM | 0.1473 mL | 0.7363 mL | 1.4727 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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