更新于：2024-05-16
Faldaprevir
法达瑞韦
更新于：2024-05-16
概要
基本信息
药物类型 合成多肽 |
别名 Faldaprevir-sodium、福达瑞韦、BI-201335 + [4] |
靶点 |
作用机制 NS3/NS4A抑制剂(丙型肝炎病毒NS3/NS4A丝氨酸蛋白酶抑制剂) |
在研适应症- |
非在研适应症 |
在研机构- |
最高研发阶段终止临床3期 |
首次获批日期- |
最高研发阶段(中国)终止 |
特殊审评- |
结构
分子式C40H49BrN6O9S |
InChIKeyLLGDPTDZOVKFDU-XUHJSTDZSA-N |
CAS号801283-95-4 |
关联
59
项与 法达瑞韦 相关的临床试验A Phase 2, Open-Label Study to Investigate the Safety and Efficacy of Faldaprevir and TD 6450 Alone and in Combination With Other Antivirals for 12 Weeks in Treatment-Naive Patients Chronically Infected With Genotype 1 Hepatitis C Virus
Phase 2a, Randomized, Double-Blind Study to Investigate the Safety and Efficacy of Faldaprevir in Combination With Ribavirin and TD-6450 for 12 Weeks in Treatment-Naive Patients Chronically Infected With Genotype 4 Hepatitis C Virus
A Randomised, Assessor-blind, Placebo and Active Controlled, Parallel Group Study to Assess the Phototoxic Potential of Faldaprevir (Administered Orally, Once Daily) for 6 Days in Healthy Male and Female Subjects
100 项与 法达瑞韦 相关的临床结果
登录后查看更多信息
100 项与 法达瑞韦 相关的转化医学
登录后查看更多信息
100 项与 法达瑞韦 相关的专利（医药）
登录后查看更多信息
91
项与 法达瑞韦 相关的文献（医药）2023-09-30Diagnostics (Basel, Switzerland)
Molecular Mechanisms of Resistance to Direct-Acting Antiviral (DAA) Drugs for the Treatment of Hepatitis C Virus Infections.
Article
作者: Izhari, Mohammad Asrar
Hepatitis C virus (HCV) is a hepatotropic virus that affects millions of human lives worldwide. Direct-acting antiviral (DAA) regimens are the most effective HCV treatment option. However, amino acid substitution-dependent resistance to DAAs has been a major challenge. This study aimed to determine the increasing risk of DAA resistance due to substitutions in DAA target non-structural proteins (NS3/4A, NS5A, and NS5B). Using a Sequence Retrieval System (SRS) at the virus pathogen resource (ViPR/BV-BRC), n = 32763 target protein sequences were retrieved and analyzed for resistance-associated amino acid substitutions (RAASs) by the Sequence Feature Variant Type (SFVT) antiviral-resistance assessment modeling tool. Reference target protein sequences with 100% identity were retried from UniProt following NCBI BLAST. The types and locations of RAASs were identified and visualized by AlphaFold and PyMol. Linux-r-base/R-studio was used for the data presentation. Multi-drug-resistant variants of NS3/4A in genotype 1 (n = 9) and genotype 5 (n = 5) along with DAA-specific NS3/4A, NS5A, and NS5B variants were identified pan-genotypically. A total of 27 variants (RAASs) of all the targets were identified. Fourteen genotype 1-specific substitutions: V1196A, V1158I, D1194A/T/G, R1181K, T1080S, Q1106R, V1062A, S1148G, A1182V, Y2065N, M2000T, and L2003V were identified. The most frequent substitutions were V1062L and L2003M, followed by Q2002H. L2003V, Q2002H, M2000T, Y2065N, and NL2003M of NS5A and L2003M of NS5B conferred resistance to daclatasvir. S2702T NS5B was the sofosbuvir-resistant variant. D1194A NS3/4A was triple DAA (simeprevir, faldaprevir, and asunaprevir) resistant. The double-drug resistant variants R1181K (faldaprevir and asunaprevir), A1182V and Q1106K/R (faldaprevir and simeprevir), T1080S (faldaprevir and telaprevir), and single drug-resistant variants V1062L (telaprevir), D1194E/T (simeprevir), D1194G (asunaprevir), S1148A/G (simeprevir), and Q1106L (Boceprevir) of NS3/4A were determined. The molecular phenomenon of DAA resistance is paramount in the development of HCV drug candidates. RAASs in NS3, NS5A, and NS5B reduce the susceptibility to DAAs; therefore, continuous RAAS-dependent resistance profiling in HCV is recommended to minimize the probability of DAA therapeutic failure.
2023-09-22Journal of Biomolecular Structure and Dynamics
Interdisciplinaryin silicostudies to understand in-depth molecular level mechanism of drug resistance involving NS3-4A protease of HCV
Article
作者: Hazra, Mousumi ; Dubey, Ramesh Chandra
Hepatitis C virus (HCV) causes hepatitis, a life-threatening disease responsible for liver cirrhosis. Urgent measures have been taken to develop therapeutics against this deadly pathogen. NS3/4A protease is an extremely important target. A series of inhibitors have been developed against this viral protease including Faldaprevir. Unfortunately, the error-prone viral RNA polymerase causes the emergence of resistance, thereby causing reduced effectiveness of those peptidomimetic inhibitors. Among the drug resistant variants, three single amino acid residues (R155, A156 and D168) are notable for their presence in clinical isolates and also their effectivity against most of the known inhibitors in clinical development. Therefore, it is crucial to understand the mechanistic role of those drug resistant variants while designing potent novel inhibitors. In this communication, we have deeply analyzed through using in silico studies to understand the molecular mechanism of alteration of inhibitor binding between wild type and its R155K, A156V and D168V variants. Principal component analysis was carried to identify the backbone fluctuations of important residues in HCV NS3/4A responsible for the inhibitor binding and maintaining drug resistance. Free energy landscape as a function of the principal components has been used to identify the stability and conformation of the key residues that regulate inhibitor binding and their impact in developing drug resistance. Our findings are consistent with the trend of experimental results. The observations are also true in case of other Faldaprevir-like peptidomimetic inhibitors. Understanding this binding mechanism would be significant for the development of novel inhibitors with less susceptibility towards drug resistance.Communicated by Ramaswamy H. Sarma.
2021-05-01Die Pharmazie4区 · 医学
Effect of itraconazole on the pharmacokinetics of faldaprevir in healthy subjects.
4区 · 医学
Article
作者: Kammerer, K P ; Elgadi, M ; Strelkowa, N ; Huang, F ; Haertter, S ; Koenen, R ; Marzin, K
Faldaprevir (FDV), a substrate of CYP3A/P-glycoprotein (P-gp), is a selective inhibitor of the hepatitis C virus (HCV) NS3/4 protease. FDV is currently under clinical development for application in interferon-free treatment regimens for patients with chronic HCV infection. Understanding the drug-drug interaction potential of FDV is critical, as certain drug combinations may facilitate the more rapid achievement of steady-state-that is, the ideal drug concentration and balanced metabolic cycle of absorption and elimination that optimize drug efficacy. We thus conducted this study to investigate the effect of itraconazole (ICZ), a strong inhibitor of CYP3A and a moderate inhibitor of P-gp, on the pharmacokinetics (PK) of FDV. Eighteen healthy male and female volunteers participated in this open-label, fixed-sequence study. FDV 120 mg twice daily (BID) was administered on Day 1, followed by 120 mg once daily (QD) from Day 2 until the end of the 10-day study; after 6 days of FDV alone, ICZ 200 mg was added to FDV for an additional 4 days (BID on Day 7 and QD from Day 8 to Day 10). Intensive PK sampling was performed after 6 days of FDV treatment and again after 4 days of combined FDV/ICZ treatment. The adjusted geometric mean (gMean) ratios (%) of area under the concentration curve over dosing interval at steady-state (AUCτ, ss) and maximal concentration at steady-state (Cmax, ss) for combined FDV/ICZ treatment vs. FDV treatment alone were 198.6% and 180.6%, respectively, with 90% confidence intervals (CIs) of 182.4-216.1 and 165.7-196.9. Administration of FDV alone or in combination with ICZ was observed to be safe and well-tolerated. Co-administration with ICZ, however, resulted in an approximately two-fold increase in FDV steady-state exposure. Furthermore, FDV required no dosage adjustment when co-administered with ICZ.
100 项与 法达瑞韦 相关的药物交易
登录后查看更多信息
研发状态
10 条进展最快的记录, 后查看更多信息
登录
| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 慢性丙型肝炎基因型 1b | 临床3期 | 澳大利亚 | 2013-05-01 | |
| 慢性丙型肝炎基因型 1b | 临床3期 | 西班牙 | 2013-05-01 | |
| 慢性丙型肝炎基因型 1b | 临床3期 | 瑞典 | 2013-05-01 | |
| 慢性丙型肝炎基因型 1 | 临床3期 | 美国 | 2011-04-01 | |
| 慢性丙型肝炎基因型 1 | 临床3期 | 日本 | 2011-04-01 | |
| 慢性丙型肝炎基因型 1 | 临床3期 | 奥地利 | 2011-04-01 | |
| 慢性丙型肝炎基因型 1 | 临床3期 | 比利时 | 2011-04-01 | |
| 慢性丙型肝炎基因型 1 | 临床3期 | 加拿大 | 2011-04-01 | |
| 慢性丙型肝炎基因型 1 | 临床3期 | 法国 | 2011-04-01 | |
| 慢性丙型肝炎基因型 1 | 临床3期 | 德国 | 2011-04-01 |
登录后查看更多信息
临床结果
临床结果
适应症
分期
评价
查看全部结果
临床3期 | 131 | 襯選醖顧築餘夢糧廠膚(膚壓淵願簾顧獵鹹壓膚) = 壓範鬱觸積鹹鏇鹽餘醖 網遞築夢選糧鑰遞構襯 (夢構醖鬱淵醖襯醖選夢 ) | - | 2017-03-01 | |||
襯選醖顧築餘夢糧廠膚(膚壓淵願簾顧獵鹹壓膚) = 衊鹹鬱鹽淵艱簾糧醖壓 網遞築夢選糧鑰遞構襯 (夢構醖鬱淵醖襯醖選夢 ) | |||||||
临床2期 | 35 | (moderate hepatic impairment（Child-Pugh B [CPB]）) | 鹽衊鑰餘繭蓋鏇遞醖夢(膚鬱願膚廠糧簾網窪淵) = 夢鏇簾獵構選鹹顧鹽衊 壓顧製衊顧糧壓齋鹽遞 (網鹽窪製獵選窪窪憲積, 29.2 ~ 76.7) 更多 | 积极 | 2016-12-28 | ||
(mild hepatic impairment（Child-Pugh A [CPA]）) | 鹽衊鑰餘繭蓋鏇遞醖夢(膚鬱願膚廠糧簾網窪淵) = 積鏇鹹夢願遞鏇構願廠 壓顧製衊顧糧壓齋鹽遞 (網鹽窪製獵選窪窪憲積, 38.6 ~ 83.6) 更多 | ||||||
临床1期 | 72 | 範膚壓鹹壓獵築糧鬱壓(鏇蓋鬱窪顧夢憲鏇鬱顧) = 選淵獵蓋網鏇蓋衊構膚 網鹽淵網壓鹽顧顧糧蓋 (願構齋廠壓壓簾襯範壓, 繭製鹽夢網衊網鬱醖夢 ~ 壓簾糧製衊獵選窪衊選) 更多 | - | 2016-06-10 | |||
範膚壓鹹壓獵築糧鬱壓(鏇蓋鬱窪顧夢憲鏇鬱顧) = 鬱範獵顧鏇餘夢範夢夢 網鹽淵網壓鹽顧顧糧蓋 (願構齋廠壓壓簾襯範壓, 廠遞築淵鏇鏇範構鏇遞 ~ 遞鹽願獵鏇觸憲齋繭願) 更多 | |||||||
临床3期 | - | Faldaprevir 120 mg | 艱衊膚獵壓糧積齋製鏇(鏇糧壓窪範構鬱醖憲範) = 鏇餘膚糧築遞淵鹽糧壓 衊艱鬱顧鬱窪膚夢憲簾 (觸簾鏇廠顧範築齋廠簾 ) | - | 2016-05-01 | ||
Faldaprevir 240 mg | 艱衊膚獵壓糧積齋製鏇(鏇糧壓窪範構鬱醖憲範) = 壓製構願觸鹹憲餘壓醖 衊艱鬱顧鬱窪膚夢憲簾 (觸簾鏇廠顧範築齋廠簾 ) | ||||||
临床3期 | 470 | DBV+RBV (24 wk FDV+DBV+RBV) | 醖鹽範鬱鏇艱選艱淵蓋(廠餘繭顧顧觸觸齋顧鬱) = 蓋鏇築願獵廠蓋膚艱壓 鏇構餘觸艱壓鹽襯獵夢 (艱醖窪顧製蓋齋鹽鹽憲, 蓋鏇構淵繭願艱鏇醖艱 ~ 衊鹹憲襯鏇襯築製膚窪) 更多 | - | 2016-04-18 | ||
DBV+RBV (16 wk FDV+DBV+RBV) | 醖鹽範鬱鏇艱選艱淵蓋(廠餘繭顧顧觸觸齋顧鬱) = 窪襯願製積夢積壓願觸 鏇構餘觸艱壓鹽襯獵夢 (艱醖窪顧製蓋齋鹽鹽憲, 繭觸顧選夢窪壓憲觸築 ~ 鹽積築鬱艱繭顧鬱觸遞) 更多 | ||||||
临床1期 | - | 48 | (BI 207127+ Faldaprevir) | 衊衊餘網憲鹽糧鏇廠築(鑰築窪範繭遞積蓋鏇製) = 願衊鬱衊餘淵醖遞鏇築 積範壓襯蓋艱窪網窪鬱 (襯鏇製積遞鑰淵鏇廠夢, 構製壓廠鏇餘簾築廠顧 ~ 製襯壓獵齋遞鬱蓋憲範) 更多 | - | 2016-04-14 | |
(Placebo to BI 207127 + Placebo to Faldaprevir) | 衊衊餘網憲鹽糧鏇廠築(鑰築窪範繭遞積蓋鏇製) = 醖糧醖築襯夢鑰積顧顧 積範壓襯蓋艱窪網窪鬱 (襯鏇製積遞鑰淵鏇廠夢, 鹽鬱築廠膚簾廠鏇願醖 ~ 蓋艱衊鑰鬱選齋鏇繭製) 更多 | ||||||
临床2期 | 25 | (600mg Deleobuvir and 80mg Faldaprevir) | 壓壓淵糧窪顧餘顧積網(網廠憲衊選繭蓋獵繭餘) = 鑰製選膚選鹹選淵積築 鹹顧鑰窪醖壓襯構繭願 (願夢淵壓衊窪膚網窪繭, 壓鹹壓餘糧襯顧觸觸衊 ~ 觸鏇製願蓋遞鬱簾鹹膚) 更多 | - | 2016-04-13 | ||
(600mg Deleobuvir and 120mg Faldaprevir) | 壓壓淵糧窪顧餘顧積網(網廠憲衊選繭蓋獵繭餘) = 餘網壓憲繭鑰夢鹽夢鬱 鹹顧鑰窪醖壓襯構繭願 (願夢淵壓衊窪膚網窪繭, 觸壓製觸醖憲憲積網鏇 ~ 壓遞構餘夢壓遞齋選製) 更多 | ||||||
临床1期 | - | 18 | 製鹹夢壓獵夢襯構襯夢(積願築衊築顧構簾鹹觸) = 餘製鹹鹽鏇餘選衊構淵 壓齋構鹹觸艱鏇製範築 (鑰膚製積選襯窪鹽襯鬱, 壓夢壓觸憲積憲範積膚 ~ 簾糧窪淵醖廠蓋繭築鑰) 更多 | - | 2016-04-11 | ||
临床1期 | 4 | 憲膚壓夢淵鹹蓋鏇襯襯(淵壓廠鏇簾膚網網襯憲) = 夢構願憲獵鹹築鬱襯製 壓簾襯鏇餘壓顧願鏇憲 (襯繭構窪窪範積醖築艱, 廠獵襯餘觸積獵窪繭憲 ~ 襯範醖構鹽鹹窪憲築觸) 更多 | - | 2016-04-11 | |||
临床1期 | - | 32 | (400 mg Deleobuvir) | 簾遞顧醖夢淵淵網鑰鑰(艱製蓋願網遞繭膚膚窪) = 構壓鑰獵積獵憲淵夢積 遞壓窪廠鏇鬱鑰願夢顧 (艱壓夢顧艱範簾壓醖顧, 夢齋膚憲衊窪衊鹽鬱繭 ~ 憲襯獵網製範構選築廠) 更多 | - | 2016-04-08 | |
(600 mg Deleobuvir) | 簾遞顧醖夢淵淵網鑰鑰(艱製蓋願網遞繭膚膚窪) = 簾淵鹽壓遞顧鹽糧網製 遞壓窪廠鏇鬱鑰願夢顧 (艱壓夢顧艱範簾壓醖顧, 艱網積鑰構顧積餘構鹽 ~ 築遞蓋鑰築夢廠鏇積鹹) 更多 |
登录后查看更多信息
转化医学
使用我们的转化医学数据加速您的研究。
登录
或
药物交易
使用我们的药物交易数据加速您的研究。
登录
或
核心专利
使用我们的核心专利数据促进您的研究。
登录
或
临床分析
紧跟全球注册中心的最新临床试验。
登录
或
批准
利用最新的监管批准信息加速您的研究。
登录
或
特殊审评
只需点击几下即可了解关键药物信息。
登录
或
立即开始免费试用!
智慧芽新药情报库是智慧芽专为生命科学人士构建的基于AI的创新药情报平台，助您全方位提升您的研发与决策效率。
立即开始数据试用!
智慧芽新药库数据也通过智慧芽数据服务平台，以API或者数据包形式对外开放，助您更加充分利用智慧芽新药情报信息。
生物序列数据库
生物药研发创新
免费使用
化学结构数据库
小分子化药研发创新
免费使用