| 规格 | 价格 | 库存 | 数量 |
|---|---|---|---|
| 2mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
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| 靶点 |
Hepatitis C virus (HCV) nonstructural protein (NS) 3/4A protease
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|---|---|
| 体外研究 (In Vitro) |
为了使 HCV 编码的多蛋白（NS3、NS4A、NS4B、NS5A 和 NS5B 蛋白的未成熟形式）被蛋白酶切割并随后进行病毒复制，需要 NS3/4A 蛋白酶[1]。在酶测定中利用反式和重组 NS3 蛋白酶结构域中提供的同基因 NS4A 肽辅因子。在表达编码海肾荧光素酶的 HCV 复制子的稳定细胞系（Huh-7-Lunet 或 Huh7-1C 细胞）中，Voxilaprevir 对 HCV 基因型 1b 和 3a[1] 的 NS3 蛋白酶的 Ki 值分别为 0.038 nM 和 0.066 nM ）。在基因型 1 至 6 中，vitilaprevir 表现出强大的全基因型抗病毒活性，EC50 范围为 0.33 至 6.6 nM。 Voxilaprevir 对 HCV 复制子株 DQ314805、H77、Con1、JFH-1、J6、J8（全长）的 IC50 值为 0.33 nM、3.9 nM、3.3 nM、3.7 nM、4.5 nM、1.8 nM 和 6.6 nM、1.9 nM 、HM568433、SA13（NS3嵌合体），分别[1]。
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| 药代性质 (ADME/PK) |
Absorption, Distribution and Excretion
When provided as the fixed dose combination product Vosevi with [DB08934] and [DB11613], voxilaprevir reaches a maximum concentration (Cmax) of 192 ng/mL at a maximum time (Tmax) of 4 hours post-dose. Voxilaprevir is primarily eliminated via biliary excretion. Metabolism / Metabolites Voxilaprevir is primarily metabolized by Cytochrome P450 3A4 (CYP3A4) and to a lesser extent by CYP2C8 and CYP1A2. Biological Half-Life 33 hr |
| 毒性/毒理 (Toxicokinetics/TK) |
Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation Voxilaprevir has not been studied in nursing mothers being treated for hepatitis C infection. Because it is greater than 99% bound to maternal plasma proteins, amounts in breastmilk are likely to be very low. Some sources recommend against breastfeeding when voxilaprevir is used with ribavirin. Hepatitis C is not transmitted through breastmilk and breastmilk has been shown to inactivate hepatitis C virus (HCV). However, the Centers for Disease Control recommends that mothers with HCV infection should consider abstaining from breastfeeding if their nipples are cracked or bleeding. It is not clear if this warning would apply to mothers who are being treated for hepatitis C. Infants born to mothers with HCV infection should be tested for HCV infection; because maternal antibody is present for the first 18 months of life and before the infant mounts an immunologic response, nucleic acid testing is recommended. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding Voxilaprevir is more than 99% bound to human plasma proteins. |
| 参考文献 | |
| 其他信息 |
Pharmacodynamics
Voxilaprevir is a direct-acting antiviral agent that targets viral NS3/4A protein and causes a decrease in serum HCV RNA levels. It disrupts HCV replication by specifically inhibiting the critical functions of NS3/4A protein in the replication complex. It does not appear to prolong the QT interval even when given at 9 times the maximum recommended dose. |
| 分子式 |
C40H52F4N6O9S
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|---|---|---|
| 分子量 |
868.94
|
|
| 精确质量 |
868.345
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| 元素分析 |
C, 55.29; H, 6.03; F, 8.75; N, 9.67; O, 16.57; S, 3.69
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| CAS号 |
1535212-07-7
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| 相关CAS号 |
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| PubChem CID |
89921642
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| 外观&性状 |
White to off-white solid powder
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| 密度 |
1.4±0.1 g/cm3
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| 折射率 |
1.596
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| LogP |
3.83
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| tPSA |
203.6
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| 氢键供体(HBD)数目 |
3
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| 氢键受体(HBA)数目 |
15
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| 可旋转键数目(RBC) |
9
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| 重原子数目 |
60
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| 分子复杂度/Complexity |
1780
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| 定义原子立体中心数目 |
8
|
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| SMILES |
S(C1(C)CC1)(NC([C@]1(C[C@H]1C(F)F)NC([C@@H]1[C@H](CC)[C@@H]2CN1C([C@H](C(C)(C)C)NC(=O)O[C@@H]1C[C@H]1CCCCC(C1C(=NC3C=C(C=CC=3N=1)OC)O2)(F)F)=O)=O)=O)(=O)=O
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| InChi Key |
MZBLZLWXUBZHSL-FZNJKFJKSA-N
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| InChi Code |
InChI=1S/C40H52F4N6O9S/c1-7-22-27-19-50(28(22)32(51)48-39(18-23(39)31(41)42)35(53)49-60(55,56)38(5)14-15-38)34(52)30(37(2,3)4)47-36(54)59-26-16-20(26)10-8-9-13-40(43,44)29-33(58-27)46-25-17-21(57-6)11-12-24(25)45-29/h11-12,17,20,22-23,26-28,30-31H,7-10,13-16,18-19H2,1-6H3,(H,47,54)(H,48,51)(H,49,53)/t20-,22-,23+,26-,27+,28+,30-,39-/m1/s1
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| 化学名 |
(33R,34S,35S,91R,92R,5S)-5-(tert-butyl)-N-((1R,2R)-2-(difluoromethyl)-1-(((1-methylcyclopropyl) sulfonyl)carbamoyl)cyclopropyl)-34-ethyl-14,14-difluoro-17-methoxy-4,7-dioxo-2,8-dioxa-6-aza-1(2,3)-quinoxalina-3(3,1)-pyrrolidina-9(1,2)-cyclopropanacyclotetradecaphane-35-carboxamide
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| 别名 |
GS-9857; GS 9857; GS9857; trade name: Vosevi
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| HS Tariff Code |
2934.99.9001
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| 存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 运输条件 |
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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| 溶解度 (体外实验) |
DMSO : ≥ 100 mg/mL (~115.08 mM)
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|---|---|
| 溶解度 (体内实验) |
配方 1 中的溶解度: ≥ 2.5 mg/mL (2.88 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL 澄清 DMSO 储备液加入900 μL 玉米油中，混合均匀。 请根据您的实验动物和给药方式选择适当的溶解配方/方案： 1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL； 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果，工作液请现配现用！ 6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
| 制备储备液 | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1508 mL | 5.7541 mL | 11.5083 mL | |
| 5 mM | 0.2302 mL | 1.1508 mL | 2.3017 mL | |
| 10 mM | 0.1151 mL | 0.5754 mL | 1.1508 mL |
1、根据实验需要选择合适的溶剂配制储备液 (母液)：对于大多数产品，InvivoChem推荐用DMSO配置母液 (比如：5、10、20mM或者10、20、50 mg/mL浓度），个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息，或者很难将产品溶解在溶液中，请联系我们;
3、建议使用下列计算器进行相关计算（摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等）;
4、母液配好之后，将其分装到常规用量，并储存在-20°C或-80°C，尽量减少反复冻融循环。
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)。如该浓度超过该批次药物DMSO溶解度，请首先与我们联系。
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 ddH2O，混匀澄清。
(1) 请确保溶液澄清之后，再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶；
(2) 一定要按顺序加入溶剂 (助溶剂) 。
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02402452 | COMPLETED | Drug: Voxilaprevir | HCV Infection | Gilead Sciences | 2015-05-05 | Phase 1 |
| NCT06180590 | RECRUITING | Drug: Sofosbuvir / Velpatasvir / Voxilaprevir Oral Tablet [Vosevi] |
Chronic Hepatitis C Medication Reaction |
The Third Affiliated Hospital of Guangzhou Medical University |
2023-02-28 | |
| NCT05717400 | RECRUITING | Drug:Bevacizumab Drug:Atezolizumab Drug:Sofosbuvir |
Liver Cancer | M.D. Anderson Cancer Center |
2023-02-07 | Phase 4 |
| NCT02397707 | COMPLETED | Drug: Voxilaprevir | HCV Infection | Gilead Sciences | 2015-03-24 | Phase 1 |
| NCT02185794 | COMPLETED | Drug:Voxilaprevir Drug:Placebo to match voxilaprevir Drug:SOF/VEL |
Hepatitis C Virus Infection | Gilead Sciences | 2014-06-13 | Phase 1 |
|
Ac-DEMEEC-OH
Faldaprevir sodium
NS5A-IN-1
NS5A-IN-2
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