Besifovir
(Synonyms: P-[[[1-[(2-氨基-9H-嘌呤-9-基)甲基]环丙基]氧基]甲基]-磷酸,LB80331) 目录号 : GC38517
Besifovir is novel and potent acyclic nucleotide phosphonate used to treat hepatitis B virus (HBV) infection.
Cas No.:441785-25-7
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
Besifovir is novel and potent acyclic nucleotide phosphonate used to treat hepatitis B virus (HBV) infection.
| Cas No. | 441785-25-7 | SDF | |
| 别名 | P-[[[1-[(2-氨基-9H-嘌呤-9-基)甲基]环丙基]氧基]甲基]-磷酸,LB80331 | ||
| Canonical SMILES | NC1=NC=C2N=CN(CC3(OCP(O)(O)=O)CC3)C2=N1 | ||
| 分子式 | C10H14N5O4P | 分子量 | 299.22 |
| 溶解度 | DMSO: 250 mg/mL (835.51 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 | 3.342 mL | 16.7101 mL | 33.4202 mL |
| 5 mM | 0.6684 mL | 3.342 mL | 6.684 mL |
| 10 mM | 0.3342 mL | 1.671 mL | 3.342 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。
Pharmacokinetic evaluation of Besifovir for the treatment of HBV infection
Expert Opin Drug Metab Toxicol 2018 Jan;14(1):101-106.PMID:29237296DOI:10.1080/17425255.2018.1417983.
Besifovir (LB80380) is a relatively new oral acyclic nucleotide phosphonate. We reviewed the pharmacokinetic characteristics of LB80380 and discussed its role in the treatment of chronic hepatitis B infection. Areas covered: LB80380 is a prodrug of LB80331 and LB80317. It is rapidly absorbed when taken orally. Escalating doses of Besifovir produce linear increase of the plasma concentration. Doses above 60mg are effective for inhibiting HBV in human. Using 60mg as an example, the maximal concentration of LB80331 in plasma is 397 ng/mL. The time required to reach maximal concentration in plasma and elimination half-life are 2.0 and 3.0 h, respectively. Besifovir and its metabolites are mainly excreted via the kidneys. Its antiviral efficacy is non-inferior to ETV 0.5mg daily. It is generally safe in terms of renal and bone toxicity. The most common adverse event is carnitine depletion which affects almost all patients on Besifovir requiring carnitine supplementation. Expert opinion: Besifovir demonstrated predictable pharmacokinetic characteristics in human subjects. Few clinical studies on Besifovir have been conducted. More data are expected particularly for special populations. The adverse events upon long term exposure should be monitored. Large scale head-to-head trials comparing Besifovir with existing NA, especially tenofovir alafenamide, should be conducted.
Besifovir therapy improves hepatic histology and reduces covalently closed circular DNA in chronic hepatitis B patients
J Gastroenterol Hepatol 2022 Feb;37(2):378-386.PMID:34653281DOI:10.1111/jgh.15710.
Background and aim: Besifovir dipivoxil maleate (BSV) was reported to have comparable antiviral efficacy and superior renal and bone safety to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients. The present study aims to evaluate changes of liver histology and intrahepatic covalently closed circular DNA (cccDNA) levels by BSV treatment in comparison with TDF therapy. Methods: This is a subset study of the phase 3 trial comparing BSV with TDF. Among them, only CHB patients willing to participate in a histologic evaluation study were enrolled. Liver histologic examination and intrahepatic cccDNA quantification were performed. Results: A total of 46 CHB patients received liver biopsies (BSV, n = 29; TDF, n = 17). After 48 weeks of treatment, virological response rate was comparable between the groups (P = 0.707). Follow-up liver biopsies showed that necroinflammation was significantly improved in the both groups. However, the histological response rate defined as the proportion of subjects whose modified histologic activity index score decreased by ≥ 2 without deterioration in fibrosis was higher in the BSV group than in the TDF group (77.8% vs 36.4%, P = 0.048). The proportion of subjects with Ishak fibrosis score 3 or more decreased from 77.7% to 55.5% in the BSV and that decreased from 72.7% to 45.4% in the TDF group. The intrahepatic cccDNA significantly decreased from baseline after 48 weeks of BSV or TDF treatment (P < 0.001) without intergroup differences (P = 0.349). Conclusions: The BSV therapy improves hepatic histology and decreases intrahepatic cccDNA in CHB patients.
Susceptibility of Drug Resistant Hepatitis B Virus Mutants to Besifovir
Biomedicines 2022 Jul 7;10(7):1637.PMID:35884942DOI:10.3390/biomedicines10071637.
Currently, interferon alpha and nucleos(t)ide analogues (NAs) are clinically available to treat hepatitis B virus (HBV) infection. Several NAs, including lamivudine (LMV), adefovir (ADV), entecavir (ETV) and tenofovir (TDF or TAF) have been approved and administered to chronic hepatitis B (CHB) patients. NAs inhibit HBV DNA synthesis by targeting the reverse transcriptase (RT) domain of HBV polymerase. Several mutations in the RT domain which lead to drug resistance against NAs have been reported, even for TDF and TAF which are highly potent with very low resistance rate. Besifovir (BFV) is a new antiviral dGMP analogue able to be used as a new NA drug for the control of CHB infection. Drug resistance to BFV is not well known due to its shorter duration of clinical use. Recently, we reported that rtL180M (M) and rtM204V (V) mutations, already resistant to LMV, are associated with BFV resistance. However, the susceptibility to BFV of previously known HBV mutants resistant to various drugs has not been studied. To investigate this, we performed in vitro drug susceptibility assays using natural and artificial mutants that are associated with resistance to LMV, ADV, ETV or TDF. As a result, LMV-resistant mutants were not susceptible to BFV and ETV-resistant clones showed partial resistance against BFV as well. However, ADV-resistant mutants were highly sensitive to BFV. In case of tenofovir-resistant mutations, the HBV mutants harboring primary mutations to tenofovir resistance were susceptible to BFV. Therefore, our study revealed that BSV may serve as an alternative drug for patients with ADV-, ETV-, TDF- or TAF-resistance.
Besifovir dipivoxil maleate: a novel antiviral agent with low toxicity and high genetic barriers for chronic hepatitis B
Expert Opin Pharmacother 2021 Dec;22(18):2427-2433.PMID:34392744DOI:10.1080/14656566.2021.1967321.
Introduction: Chronic hepatitis B is an important public health concern. Introduction of oral nucleos(t)ide analogs (NAs), inhibitors of hepatitis B virus (HBV) polymerase, was a milestone that lowered the high viral loads associated with an increased risk of liver-related complications. Areas covered: Although the currently available NAs are effective in suppressing viral replication, anti-HBV treatment in principle requires lifelong drug administration, and some patients have limitations such as the incidence of liver cancer and the likelihood of toxicities following long-term treatment despite viral suppression. Besifovir dipivoxil maleate (BSV), an oral nucleotide analog, is a prodrug that is metabolized to its active form. It has consistent and well-characterized pharmacokinetics in animals and human. In clinical studies, BSV exhibits significant and potent viral suppression of HBV replication with maintenance of antiviral efficacy for over 192 weeks without resistance, or renal and bone toxicities. Herein, the authors discuss the data of BSV and provide the reader with their expert opinion. Expert opinion: BSV is a newly developed antiviral agent against HBV. This new agent has strong antiviral activity with low toxicity and a high barrier to resistance. Because there is concern that patients treated with a high dose of BSV require carnitine supplementation, BSV with carnitine supplementation is recommended during antiviral therapy.
Continuing Besifovir dipivoxil maleate versus switching from tenofovir disoproxil fumarate for treatment of chronic hepatitis B: Results of 192-week phase 3 trial
Clin Mol Hepatol 2021 Apr;27(2):346-359.PMID:33493393DOI:10.3350/cmh.2020.0307.
Background/aims: Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. Methods: Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). Results: Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. Conclusion: BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).