GLP-26
目录号 : GC38785
GLP-26 是一种 HBV 衣壳组装调节剂 (CAM)，抑制 Hep AD38 系统中的 HBV DNA 复制 (IC50=3 nM)， 并在 1 μM 时使 cccDNA 降低> 90％。GLP-26 破坏前基因组 RNA 的衣壳化，导致核衣壳解体，并减少 cccDNA 库。
Cas No.:2133017-36-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
GLP-26 is a HBV capsid assembly modulators (CAM), inhibits HBV DNA replication in Hep AD38 system (IC50=3 nM), and reduces cccDNA by >90% at 1 μM.GLP-26 disrupts the encapsidation of pre-genomic RNA, causes nucleocapsid disassembly and reduces cccDNA pools[1].
GLP-26 (0.7-1.7 μM; 3 days) reduces secreted HBeAg in HepNTCP-DL cells transfected with HBVwild type, with EC50 values of 0.7 μM[2]. Cell Viability Assay[2] Cell Line: HepNTCP-DL cells
[1]. Nijampatnam B, et al. Recent advances in the development of HBV capsid assembly modulators. Curr Opin Chem Biol. 2019 Jun;50:73-79.
| Cas No. | 2133017-36-2 | SDF | |
| Canonical SMILES | O=C(C1=C(C)C(C(C(NCC#C)=O)=O)=C(C)N1C)NC2=CC=C(F)C(F)=C2 | ||
| 分子式 | C19H17F2N3O3 | 分子量 | 373.35 |
| 溶解度 | DMSO: 125 mg/mL (334.81 mM) | 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 | 2.6785 mL | 13.3923 mL | 26.7845 mL |
| 5 mM | 0.5357 mL | 2.6785 mL | 5.3569 mL |
| 10 mM | 0.2678 mL | 1.3392 mL | 2.6785 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。
Studies on the Efficacy, Potential Cardiotoxicity and Monkey Pharmacokinetics of GLP-26 as a Potent Hepatitis B Virus Capsid Assembly Modulator
Viruses 2021 Jan 15;13(1):114.PMID:33467678DOI:10.3390/v13010114.
While treatment options are available for hepatitis B virus (HBV), there is currently no cure. Anti-HBV nucleoside analogs and interferon-alpha 2b rarely clear HBV covalently closed circular DNA (cccDNA), requiring lifelong treatment. Recently, we identified GLP-26, a glyoxamide derivative which modulates HBV capsid assembly. The impact of GLP-26 on viral replication and integrated DNA was assessed in an HBV nude mouse model bearing HBV transfected AD38 xenografts. At day 45 post-infection, GLP-26 reduced HBV titers by 2.3-3 log10 versus infected placebo-treated mice. Combination therapy with GLP-26 and entecavir reduced HBV log10 titers by 4.6-fold versus placebo. Next, we examined the pharmacokinetics (PK) in cynomolgus monkeys administered GLP-26 via IV (1 mg/kg) or PO (5 mg/kg). GLP-26 was found to have 34% oral bioavailability, with a mean input time of 3.17 h. The oral dose produced a mean peak plasma concentration of 380.7 ng/mL, observed 0.67 h after administration (~30-fold > in vitro EC90 corrected for protein binding), with a mean terminal elimination half-life of 2.4 h and a mean area under the plasma concentration versus time curve of 1660 ng·hr/mL. GLP-26 was 86.7% bound in monkey plasma. Lastly, GLP-26 demonstrated a favorable toxicity profile confirmed in primary human cardiomyocytes. Thus, GLP-26 warrants further preclinical development as an add on to treatment for HBV infection.
Discovery and structure activity relationship of glyoxamide derivatives as anti-hepatitis B virus agents
Bioorg Med Chem 2021 Feb 1;31:115952.PMID:33421915DOI:10.1016/j.bmc.2020.115952.
Chronic hepatitis B viral infection is a significant health problem world-wide, and currently available antiviral agents suppress HBV infections, but rarely cure this disease. It is presumed that antiviral agents that target the viral nuclear reservoir of transcriptionally active cccDNA may eliminate HBV infection. Through a series of chemical optimization, we identified a new series of glyoxamide derivatives affecting HBV nucleocapsid formation and cccDNA maintenance at low nanomolar levels. Among all the compounds synthesized, GLP-26 displays a major effect on HBV DNA, HBeAg secretion and cccDNA amplification. In addition, GLP-26 shows a promising pre-clinical profile and long-term effect on viral loads in a humanized mouse model.
Assessment of a Computational Approach to Predict Drug Resistance Mutations for HIV, HBV and SARS-CoV-2
Molecules 2022 Aug 24;27(17):5413.PMID:36080181DOI:10.3390/molecules27175413.
Viral resistance is a worldwide problem mitigating the effectiveness of antiviral drugs. Mutations in the drug-targeting proteins are the primary mechanism for the emergence of drug resistance. It is essential to identify the drug resistance mutations to elucidate the mechanism of resistance and to suggest promising treatment strategies to counter the drug resistance. However, experimental identification of drug resistance mutations is challenging, laborious and time-consuming. Hence, effective and time-saving computational structure-based approaches for predicting drug resistance mutations are essential and are of high interest in drug discovery research. However, these approaches are dependent on accurate estimation of binding free energies which indirectly correlate to the computational cost. Towards this goal, we developed a computational workflow to predict drug resistance mutations for any viral proteins where the structure is known. This approach can qualitatively predict the change in binding free energies due to mutations through residue scanning and Prime MM-GBSA calculations. To test the approach, we predicted resistance mutations in HIV-RT selected by (-)-FTC and demonstrated accurate identification of the clinical mutations. Furthermore, we predicted resistance mutations in HBV core protein for GLP-26 and in SARS-CoV-2 3CLpro for nirmatrelvir. Mutagenesis experiments were performed on two predicted resistance and three predicted sensitivity mutations in HBV core protein for GLP-26, corroborating the accuracy of the predictions.
Novel Hepatitis B Virus Capsid Assembly Modulator Induces Potent Antiviral Responses In Vitro and in Humanized Mice
Antimicrob Agents Chemother 2020 Jan 27;64(2):e01701-19.PMID:31712213DOI:10.1128/AAC.01701-19.
Hepatitis B virus (HBV) affects an estimated 250 million chronic carriers worldwide. Though several vaccines exist, they are ineffective for those already infected. HBV persists due to the formation of covalently closed circular DNA (cccDNA)-the viral minichromosome-in the nucleus of hepatocytes. Current nucleoside analogs and interferon therapies rarely clear cccDNA, requiring lifelong treatment. Our group identified GLP-26, a novel glyoxamide derivative that alters HBV nucleocapsid assembly and prevents viral DNA replication. GLP-26 exhibited single-digit nanomolar anti-HBV activity, inhibition of HBV e antigen (HBeAg) secretion, and reduced cccDNA amplification, in addition to showing a promising preclinical profile. Strikingly, long term combination treatment with entecavir in a humanized mouse model induced a decrease in viral loads and viral antigens that was sustained for up to 12 weeks after treatment cessation.