Bictegravir (GS-9883) 是一种用于治疗人类免疫缺陷病毒1型（HIV-1）感染的整合酶链转移抑制剂（INSTI）。
Cas No.:1611493-60-7
Sample solution is provided at 25 µL, 10mM.
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Bictegravir (GS-9883) is an integrase strand transfer inhibitor (INSTI) used for the treatment of human immunodeficiency virus type 1 (HIV-1) infection[1]. By selectively inhibiting the strand transfer activity of HIV-1 integrase, Bictegravir effectively blocks the integration of viral DNA into the host genome, thereby exerting its antiviral effect[2]. Bictegravir demonstrates a significantly higher inhibitory potency (IC50=7.5nM) against HIV-1 integrase strand transfer activity compared to its inhibition of the integrase's 3'-processing activity, indicating high selectivity, and it exhibits potent antiviral activity across various cell types[3-4].
In vitro, treatment of the human hepatoblastoma cell line Hep3B with Bictegravir (1–20μM) for 48 hours significantly reduced cellular glucose uptake and induced mitochondrial dysfunction, leading to mitochondrial stress[5]. Bictegravir (0.01–1000nM) treatment of NL4.3 recombinant viruses carrying combinations of HIV-1 integrase mutations, cultured in GFP-reporter CD4+ T cells for 3 days, significantly inhibited viral replication activity[6].
In vivo, daily oral self-administration of Bictegravir (0.375mg) in combination with Emtricitabine (1.23mg) and Tenofovir Alafenamide (0.15375mg) to EcoHIV-infected mice for 5 weeks significantly reduced CXCL1/KC expression in the nucleus accumbens and altered peripheral immune factor levels[7]. Oral administration of Bictegravir (5mg/kg/day) via peanut butter pellets to C57BL/6 mice for 14 days significantly decreased the mRNA expression of tight junction proteins Tjp1 and Ocln in brain capillaries and downregulated the gene expression of drug efflux transporters Abcb1a and Abcg2[8].
References:
[1] Spagnuolo V, Castagna A, Lazzarin A. Bictegravir. Curr Opin HIV AIDS. 2018 Jul;13(4):326-333.
[2] Markham A. Bictegravir: First Global Approval. Drugs. 2018 Apr;78(5):601-606.
[3] Tsiang M, Jones GS, Goldsmith J, et al. Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile. Antimicrob Agents Chemother. 2016 Nov 21;60(12):7086-7097.
[4] Smith SJ, Zhao XZ, Passos DO, et al. HIV-1 Integrase Inhibitors That Are Active against Drug-Resistant Integrase Mutants. Antimicrob Agents Chemother. 2020 Aug 20;64(9):e00611-20.
[5] García-Martínez P, Gisbert-Ferrándiz L, Álvarez Á, et al. Bictegravir alters glucose tolerance in vivo and causes hepatic mitochondrial dysfunction. Antiviral Res. 2024 Nov;231:106020.
[6] Cheung PK, Shahid A, Dong W, et al. Impact of combinations of clinically observed HIV integrase mutations on phenotypic resistance to integrase strand transfer inhibitors (INSTIs): a molecular study. J Antimicrob Chemother. 2022 Mar 31;77(4):979-988.
[7] Xie Q, Namba MD, Buck LA, et al. Effects of Antiretroviral Treatment on Central and Peripheral Immune Response in Mice with EcoHIV Infection. Cells. 2024 May 20;13(10):882.
[8] Huang C, Hoque T, Bendayan R. Antiretroviral drugs efavirenz, dolutegravir and bictegravir dysregulate blood-brain barrier integrity and function. Front Pharmacol. 2023 Mar 8;14:1118580.
Bictegravir (GS-9883) 是一种用于治疗人类免疫缺陷病毒1型（HIV-1）感染的整合酶链转移抑制剂（INSTI）[1]。Bictegravir通过选择性抑制HIV-1整合酶的链转移活性，有效阻断病毒DNA整合入宿主基因组，从而发挥抗病毒作用[2]。Bictegravir对HIV-1整合酶链转移活性的抑制效力（IC50为7.5nM）远高于其对整合酶3’-加工活性的抑制，展现出高度的选择性，且在多种细胞中均表现出强效的抗病毒活性[3-4]。
在体外，Bictegravir (1–20μM) 处理人肝癌细胞系Hep3B细胞48小时，显著降低细胞对葡萄糖的摄取，并引起线粒体功能障碍，诱导线粒体应激[5]。Bictegravir (0.01–1000nM) 处理携带HIV-1整合酶突变组合的NL4.3重组病毒，在GFP报告CD4+ T细胞中培养3天，Bictegravir显著抑制病毒复制活性[6]。
在体内，Bictegravir（0.375mg）联合Emtricitabine（1.23mg）和Tenofovir Alafenamide（0.15375mg）通过口服自给药方式每日处理EcoHIV感染小鼠，持续5周，显著降低了伏隔核中CXCL1/KC的表达并改变了外周免疫因子水平[7]。Bictegravir（5mg/kg/day）通过花生酱丸剂口服给药处理C57BL/6小鼠14天，显著降低了脑毛细血管中紧密连接蛋白Tjp1和Ocln的mRNA表达，并下调了药物外排转运蛋白Abcb1a和Abcg2的基因表达[8]。
| Cell experiment [1]: | |
Cell lines | Hep3B cells(human hepatoblastoma cell line) |
Preparation Method | Hep3B cells were cultured in MEM supplemented with 10% heat-inactivated fetal bovine serum(hi-FBS), 1x non-essential amino acid solution, 2mM L-glutamine, and 1mM sodium pyruvate at 37°C, 5% CO₂. Cells were treated with Bictegravir at clinically relevant concentrations(1-20μM) for 48 hours. |
Reaction Conditions | 1-20μM; 48h |
Applications | Bictegravir significantly reduced hepatocyte glucose uptake in a concentration-dependent manner, both under basal conditions and post-insulin stimulation. Bictegravir treatment altered the mRNA expression of enzymes related to glucose metabolism, including increased G6PC1 and decreased GYS2. Furthermore, Bictegravir induced mitochondrial dysfunction, characterized by increased reactive oxygen species(ROS) production, mitochondrial membrane hyperpolarization, and enhanced cellular granularity. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice |
Preparation Method | Mice were orally administered Bictegravir (5mg/kg/day) formulated into peanut butter pellets once daily for 14 days. Control mice received vehicle pellets. At 24 hours following the final dose, mice were subjected to a sodium fluorescein (NaF) permeability assay to assess blood-brain barrier integrity. |
Dosage form | 5mg/kg/day; oral (peanut butter pellet) |
Applications | Chronic Bictegravir treatment resulted in a non-significant trend towards increased blood-brain barrier permeability. Analysis of brain capillaries isolated from treated mice showed significant downregulation of tight junction proteins Tjp1 and Ocln mRNA expression. Bictegravir also induced downregulation of drug efflux transporters Abcb1a and Abcg2 mRNA. |
References: | |
| Cas No. | 1611493-60-7 | SDF | |
| 别名 | 比克替拉韦,GS-9883 | ||
| Canonical SMILES | O=C1N([C@](CC2)([H])C[C@]2([H])O3)[C@@]3([H])CN(C=C(C(NCC(C(F)=CC(F)=C4)=C4F)=O)C5=O)C1=C5O | ||
| 分子式 | C21H18F3N3O5 | 分子量 | 449.38 |
| 溶解度 | DMSO : 83.3 mg/mL (185.37 mM) | 储存条件 | 4°C, away from moisture and light |
| 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 | 2.2253 mL | 11.1264 mL | 22.2529 mL |
| 5 mM | 445.1 μL | 2.2253 mL | 4.4506 mL |
| 10 mM | 222.5 μL | 1.1126 mL | 2.2253 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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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，
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1. 首先保证母液是澄清的；
2.
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