HBF-0259
目录号 : GC63003
HBF-0259 是一种有效和选择性的乙型肝炎病毒 (HBV) 表面抗原 (HBsAg) 分泌抑制剂，在 HepG2.2.15 细胞中的 EC50 值为 1.5 μM。HBF-0259 对 HBV DNA 合成没有影响。
Cas No.:957011-15-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
HBF-0259 is a potent and selective inhibitor of hepatitis B virus (HBV) surface antigen (HBsAg) secretion, with an EC50 of 1.5 μM in HepG2.2.15 cells. HBF-0259 has no effect on HBV DNA synthesis[1][2].
HBF-0259 (0.0158-50.0 μM) inhibits the HBsAg secretion (EC50=1.5 μM) in HepDE19 cells, with an CC50 of >50 μM[1].HBF-0259 (2-8 μM) significantly reduces the abundance of both L and M in the supernatants of HepG2.2.15 cells[1].
[1]. Dougherty AM, et, al. A substituted tetrahydro-tetrazolo-pyrimidine is a specific and novel inhibitor of hepatitis B virus surface antigen secretion. Antimicrob Agents Chemother. 2007 Dec;51(12):4427-37.
[2]. Yu W, et, al. Design, synthesis, and biological evaluation of triazolo-pyrimidine derivatives as novel inhibitors of hepatitis B virus surface antigen (HBsAg) secretion. J Med Chem. 2011 Aug 25;54(16):5660-70.
| Cas No. | 957011-15-3 | SDF | |
| 分子式 | C16H12Cl2FN5 | 分子量 | 364.2 |
| 溶解度 | DMSO : 250 mg/mL (686.44 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.7457 mL | 13.7287 mL | 27.4574 mL |
| 5 mM | 0.5491 mL | 2.7457 mL | 5.4915 mL |
| 10 mM | 0.2746 mL | 1.3729 mL | 2.7457 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Prediction of HBF-0259 interactions with hepatitis B Virus receptors and surface antigen secretory factors
Virusdisease 2016 Sep;27(3):234-241.PMID:28466034DOI:10.1007/s13337-016-0333-9.
Hepatitis B virus (HBV) is an etiological agent of viral hepatitis, which may lead to cirrhosis, and hepatocellular carcinoma. Current treatment strategies have not shown promising effect to date but various complications such as, drug toxicity-resistance have been reported. Study on newly discovered compounds, with minimal side effects, as specific HBV inhibitors is a fundamental subject introducing new biologic drugs. Here, we aimed to, by prediction, estimate interactions of HBF-0259 as a non-toxic anti-HBV compound on inhibiting the HBV through either interaction with the viral entry or HBsAg secreting factors using In Silico procedure. Molecular docking was performed by Hex 8.0.0 software to predict the interaction energy (Etot) between HBF-0259 and known cellular factors involved in HBV entry and HBsAg secreting factors. Hex 8.0.0 also employed to create protein-protein complexes. These interactions were then used to analyze the binding site of HBF-0259 within the assumed receptors by MGLTools software. Finally, the amino acid sequences involved in this interaction were aligned for any conservancy. Here, we showed that HBF-0259 Etot with CypA (-545.41 kcal/mol) and SCCA1 (499.68 kcal/mol), involved in HBsAg secretion and HBV integration, respectively, was higher than other interactions. Furthermore, HBF-0259 predicted interaction energy was even higher than those of CypA inhibitors. In addition, we claim that preS1 and/or preS2 regions within HBsAg are not suitable targets for HBF-0259. HBF-0259 has higher interaction energy with CypA and SCCA1, even more than other known receptors, co-receptors, viral ligands, and secretory factors. HBF-0259 could be introduced as potent anti-viral compound in which CypA and or SCCA1, as previously shown, are involved.
A substituted tetrahydro-tetrazolo-pyrimidine is a specific and novel inhibitor of hepatitis B virus surface antigen secretion
Antimicrob Agents Chemother 2007 Dec;51(12):4427-37.PMID:17875990DOI:10.1128/AAC.00541-07.
The high levels of hepatitis B virus (HBV) surface antigen (HBsAg)-bearing subviral particles in the serum of chronically infected individuals are thought to play a role in suppressing the HBV-specific immune response. Current therapeutics are not directed at reducing this viral antigenemia; thus, our group has focused on identifying inhibitors of HBsAg secretion. By using the HBV-expressing cell line HepG2.2.15, high-throughput screening of an 80,288-compound synthetic small-molecule library identified HBF-0259, an aromatically substituted tetrahydro-tetrazolo-(1, 5-a)-pyrimidine. Following resynthesis, HBF-0259 had a 50% effective concentration of approximately 1.5 microM in a secondary, HBV-expressing cell line, with a concentration that exhibited 50% cytotoxicity of >50 microM. The equilibrium concentration of HBF-0259 in aqueous solution at physiological pH was 15 to 16 microM; the selective index was thus >9. As intended by our screening paradigm, HBF-0259 is a selective, potent inhibitor of secretion of both subviral and DNA-containing viral particles, while the secretion of alpha-1-acid glycoprotein and alpha-1-antitrypsin was unaffected. The HBV e antigen, which is not a constituent of HBV particles, was also unaffected, suggesting that the secretion of particles bearing HBV structural glycoproteins is targeted directly. Inhibitory activity was also confirmed by transfection of HBsAg, indicating that the action of the compound is independent of those of other viral proteins. HBF-0259 had no effect on HBV DNA synthesis, demonstrating that inhibition is independent of viral genomic replication. Finally, HBF-0259 had little or no effect on the cell-to-cell spread of two unrelated viruses, suggesting that it is a specific inhibitor of secretion of HBsAg. Possible mechanisms of action and the implications for its development are discussed.
Design, synthesis, and biological evaluation of triazolo-pyrimidine derivatives as novel inhibitors of hepatitis B virus surface antigen (HBsAg) secretion
J Med Chem 2011 Aug 25;54(16):5660-70.PMID:21786803DOI:10.1021/jm200696v.
The high levels of hepatitis B virus (HBV) surface antigen (HBsAg)-bearing subviral particles in the serum of chronically infected individuals play an important role in suppressing HBV-specific immune response and are only mildly affected by the current small molecule therapies. Thus, a therapy that specifically reduces HBsAg serum levels could be used in combination therapy with nucleos(t)ide drugs or permit therapeutic vaccination for the treatment of HBV infection. Herein, we report the design, synthesis, and evaluation of novel triazolo-pyrimidine inhibitors (1, 3, and 4) of HBsAg cellular secretion, with activity against drug-resistant HBV variants. Extensive SAR led to substantial improvements in the EC(50) of the parent compound, 5 (HBF-0259), with the best being 3c, with EC(50) = 1.4 ± 0.4 μM, SI ≥ 36. The lead candidates, both 1a (PBHBV-001) and 3c (PBHBV-2-15), were well-tolerated in both normal and HBV-transgenic mice and exhibited acceptable pharmacokinetics and bioavailability in Sprague-Dawley rats.