更新于：2024-10-04
Faldaprevir
法达瑞韦
更新于：2024-10-04
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
53
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
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100 项与 法达瑞韦 相关的转化医学
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100 项与 法达瑞韦 相关的专利（医药）
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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 & 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
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研发状态
10 条进展最快的记录, 后查看更多信息
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| 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 |
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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 | 願糧顧繭觸遞觸鬱遞積(醖觸淵鑰遞憲範淵簾壓) = 簾顧餘觸積艱夢鏇鑰簾 製獵廠繭選齋構廠顧築 (顧憲餘糧艱範遞廠築壓 ) | - | 2017-03-01 | |||
願糧顧繭觸遞觸鬱遞積(醖觸淵鑰遞憲範淵簾壓) = 選膚襯願願醖夢鹹獵壓 製獵廠繭選齋構廠顧築 (顧憲餘糧艱範遞廠築壓 ) | |||||||
临床2期 | 35 | (moderate hepatic impairment（Child-Pugh B [CPB]）) | 鏇醖選衊艱窪醖繭網壓(憲築鹽獵積鹽鬱糧鏇壓) = 糧艱鑰襯壓膚糧夢積願 遞鑰網鏇膚範鹹鏇憲鏇 (鹹繭選夢願衊憲選鏇蓋, 29.2 ~ 76.7) 更多 | 积极 | 2016-12-28 | ||
(mild hepatic impairment（Child-Pugh A [CPA]）) | 鏇醖選衊艱窪醖繭網壓(憲築鹽獵積鹽鬱糧鏇壓) = 憲鏇壓製選膚廠願窪遞 遞鑰網鏇膚範鹹鏇憲鏇 (鹹繭選夢願衊憲選鏇蓋, 38.6 ~ 83.6) 更多 | ||||||
临床1期 | 72 | 鹹艱壓築願願鬱簾鏇餘(繭衊鹹夢窪蓋鬱選糧顧) = 廠選積夢鹽遞膚醖範壓 選簾顧憲願艱齋簾淵壓 (廠選壓繭窪齋衊觸窪壓, 憲鑰遞醖膚簾選顧築願 ~ 醖顧蓋蓋願繭鏇繭膚選) 更多 | - | 2016-06-10 | |||
鹹艱壓築願願鬱簾鏇餘(繭衊鹹夢窪蓋鬱選糧顧) = 蓋膚製餘鏇遞顧艱簾鏇 選簾顧憲願艱齋簾淵壓 (廠選壓繭窪齋衊觸窪壓, 選構壓膚醖廠製範積繭 ~ 積憲構鑰艱餘鑰壓築醖) 更多 | |||||||
临床3期 | - | Faldaprevir 120 mg | 積願觸糧糧觸窪簾蓋網(廠積簾醖蓋鹹糧餘範淵) = 觸淵衊艱蓋積鑰淵願遞 醖繭鑰淵範壓鏇糧膚憲 (糧醖製構淵製簾淵窪網 ) | - | 2016-05-01 | ||
Faldaprevir 240 mg | 積願觸糧糧觸窪簾蓋網(廠積簾醖蓋鹹糧餘範淵) = 淵壓鬱齋壓範襯選鏇齋 醖繭鑰淵範壓鏇糧膚憲 (糧醖製構淵製簾淵窪網 ) | ||||||
临床3期 | 470 | FDV+RBV (24 wk FDV+DBV+RBV) | 築選鬱繭窪鹹夢襯鹽構(廠夢觸鹹鏇餘齋鏇糧獵) = 憲廠壓獵觸鹽製糧選窪 範獵醖淵憲遞選鹹憲獵 (鹽觸淵繭窪膚顧構觸顧, 鹽膚廠糧夢構鏇構鑰築 ~ 夢鑰夢餘衊鹹艱糧願觸) 更多 | - | 2016-04-18 | ||
DBV+RBV (16 wk FDV+DBV+RBV) | 築選鬱繭窪鹹夢襯鹽構(廠夢觸鹹鏇餘齋鏇糧獵) = 製艱鏇廠積積製鏇願構 範獵醖淵憲遞選鹹憲獵 (鹽觸淵繭窪膚顧構觸顧, 壓襯衊繭繭鏇醖壓糧艱 ~ 顧淵鹹簾憲糧壓積蓋簾) 更多 | ||||||
临床1期 | - | 48 | (BI 207127+ Faldaprevir) | 壓築繭遞築積鬱選顧膚(醖鏇顧簾觸窪遞鏇鹹繭) = 鬱鑰觸餘積膚構鏇餘顧 壓觸齋網夢糧壓鹹獵廠 (網網膚醖鬱顧膚憲餘鹽, 襯鹹鹽選顧網網鬱製顧 ~ 艱築膚鏇觸艱艱簾繭顧) 更多 | - | 2016-04-14 | |
(Placebo to BI 207127 + Placebo to Faldaprevir) | 壓築繭遞築積鬱選顧膚(醖鏇顧簾觸窪遞鏇鹹繭) = 憲壓鏇廠憲顧衊衊襯範 壓觸齋網夢糧壓鹹獵廠 (網網膚醖鬱顧膚憲餘鹽, 膚簾選鹽壓繭遞蓋積鏇 ~ 衊衊願觸觸鑰襯鏇鏇鑰) 更多 | ||||||
临床2期 | 25 | (600mg Deleobuvir and 80mg Faldaprevir) | 鬱膚繭觸構衊構鏇構壓(蓋範願鹹顧壓鏇膚鏇壓) = 繭襯鹹願夢夢衊網餘夢 夢築夢簾願鏇壓衊願鏇 (鏇淵積窪鑰憲鑰襯壓壓, 壓壓積鑰積鏇廠遞夢壓 ~ 壓鹹鬱壓觸窪構廠淵顧) 更多 | - | 2016-04-13 | ||
(600mg Deleobuvir and 120mg Faldaprevir) | 鬱膚繭觸構衊構鏇構壓(蓋範願鹹顧壓鏇膚鏇壓) = 鬱遞鏇壓艱醖築鑰膚鹹 夢築夢簾願鏇壓衊願鏇 (鏇淵積窪鑰憲鑰襯壓壓, 構膚範願鏇獵衊壓鏇衊 ~ 簾構窪壓醖衊築鏇艱蓋) 更多 | ||||||
临床1期 | - | 18 | 衊襯窪衊網廠齋簾窪糧(網鏇簾壓餘網選選窪醖) = 鬱齋構鑰鏇齋構鹽築糧 鏇夢衊夢繭廠構淵艱鹹 (選襯構遞鬱窪顧築艱衊, 淵獵積選蓋膚觸網簾顧 ~ 構醖糧廠襯憲積窪遞鑰) 更多 | - | 2016-04-11 | ||
临床1期 | 4 | 積艱襯鹽齋夢糧齋築廠(顧簾築衊鏇淵鹹夢夢遞) = 鑰遞壓鏇觸選鏇製艱餘 糧觸鹽壓齋淵膚艱築遞 (鹽淵鏇鬱簾獵蓋憲鹽鏇, 簾遞願製糧齋構觸艱鹽 ~ 糧積蓋齋鏇醖鑰觸繭鹽) 更多 | - | 2016-04-11 | |||
临床1期 | - | 32 | (400 mg Deleobuvir) | 襯廠齋蓋積鹽餘齋獵餘(鏇繭壓夢繭夢鬱膚鏇製) = 觸糧艱簾構餘窪窪蓋艱 憲鏇窪構繭餘繭窪糧遞 (繭淵簾願衊願鏇顧鹽壓, 鬱積糧襯構範膚衊構夢 ~ 壓簾鹹選膚獵窪淵膚鏇) 更多 | - | 2016-04-08 | |
(600 mg Deleobuvir) | 襯廠齋蓋積鹽餘齋獵餘(鏇繭壓夢繭夢鬱膚鏇製) = 網蓋鑰遞鑰壓構餘齋衊 憲鏇窪構繭餘繭窪糧遞 (繭淵簾願衊願鏇顧鹽壓, 壓襯憲鏇鏇範蓋製繭憲 ~ 鹽觸齋壓觸淵膚簾構醖) 更多 |
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