预约演示
更新于：2026-02-27
Lonafarnib
洛那法尼
更新于：2026-02-27
概要
基本信息
最高研发阶段批准上市 |
首次获批日期 美国 (2020-11-20), |
最高研发阶段(中国)临床前 |
特殊审评孤儿药 (美国)、孤儿药 (日本)、突破性疗法 (美国) |
登录后查看时间轴
结构/序列
分子式C27H31Br2ClN4O2 |
InChIKeyDHMTURDWPRKSOA-RUZDIDTESA-N |
CAS号193275-84-2 |
关联
38
项与 洛那法尼 相关的临床试验NCT06775041
A Phase 2a, Randomized, Open-Label Study to Determine the Optimal Dose and Evaluate the Safety, Tolerability, and Pharmacokinetics of Progerinin in Patients With Hutchinson-Gilford Progeria Syndrome (HGPS)
NCT05953545
Open Label Phase 2 Clinical Study of Peginterferon Lambda and Lonafarnib Boosted With Ritonavir 48-Week Combination Therapy for Delta Hepatitis
ChiCTR2100050052
Observational study of Lonafarnib in Chinese patients with progeria and progeroid laminopathy
100 项与 洛那法尼 相关的临床结果
登录后查看更多信息
100 项与 洛那法尼 相关的转化医学
登录后查看更多信息
100 项与 洛那法尼 相关的专利（医药）
登录后查看更多信息
277
项与 洛那法尼 相关的文献（医药）2026-02-01ANTICANCER RESEARCH
Targeted Sensitization of Leukemic T-cells to Anticancer Drugs by SIRT1 Agonist SRT-1720.
Article
作者: Ivanova, Donika ; Bakalova, Rumiana ; Getsov, Plamen ; Lazarova, Dessislava ; Nikolova, Biliana ; Hadjidekov, Vasil ; Zhelev, Zhivko
BACKGROUND/AIM:
Leukemia therapy targets multiple molecular pathways, including non-oncogenic but clinically relevant factors such as Silent Information Regulator 1 (SIRT1), which acts either as a tumor suppressor or tumor promoter depending on its downstream targets, cancer type, and disease stage. Although small-molecule SIRT1 activators such as SRT-1720 have shown anticancer potential, their molecular mechanisms in leukemia remain insufficiently understood. This study aimed to elucidate the effects of SRT-1720 on the redox state and viability of leukemic lymphocytes and normal lymphocytes, as well as its ability to sensitize leukemic cells to anticancer drugs.
MATERIALS AND METHODS:
The synergistic, additive or antagonistic antiproliferative effects of SRT-1720 and anticancer drugs were examined. The following parameters were analyzed: cell viability and proliferation - by trypan blue staining; apoptosis - by phosphatidylserine expression on the cell surface; and oxidative stress - by detecting intracellular levels of reactive oxygen species (ROS) and protein carbonyl products.
RESULTS:
SRT-1720 potentiated the effects of most anticancer drugs in leukemic lymphocytes. Synergism was found in combination with: barasertib, bortezomib, cisplatin, MG-132, bleomycin, ABT-737, lonafarnib, everolimus, and palbociclib. SRT-1720 increased the tolerance of normal lymphocytes to anticancer drugs, as demonstrated for everolimus, barasertib, and doxorubicin. The synergistic cytotoxicity of SRT-1720 in combination with everolimus and barasertib was accompanied by overproduction of ROS and increased induction of apoptosis in leukemic lymphocytes, but not in normal lymphocytes. SRT-1720 favorably affected the viability of normal lymphocytes, reducing oxidative stress and cytotoxicity induced by doxorubicin at the concentrations used in our study.
CONCLUSION:
SRT-1720 induces oxidative stress and apoptosis in leukemic lymphocytes through SIRT1-independent pathway(s). In contrast, it enhances antioxidant defense in normal lymphocytes through a SIRT1-dependent pathway. These findings highlight the potential of SRT-1720 as an adjuvant to chemotherapy in T-ALL, particularly in drug combinations demonstrating strong synergism, which may allow dose reduction and decreased toxicity.
2026-01-20JOURNAL OF VIROLOGY
Molecular mechanism of resistance to lonafarnib conferred by mutations in the cysteine-rich region of respiratory syncytial virus fusion glycoprotein and discovery of a lonafarnib-derived antiviral PROTAC
Article
作者: Tang, Wei ; Xue, Bao ; Xu, Xi ; Zou, Jingjing ; Zhang, Wei ; Zhang, Qiong ; Zhou, Yuan ; Yang, Kaixin ; Zhong, Jiayi ; Shang, Jinsai ; Xiao, Qingyu ; Ye, Wencai ; Mao, Yuhan ; Yang, Qi ; Zhou, Anqi ; Li, Yixue ; Tang, Jielin ; Chen, Xinwen ; Peng, Wei ; Li, Zhiyu ; Qiu, Xianjie ; Zou, Gang
ABSTRACT:
Lonafarnib, an oral antiviral that targets the fusion glycoprotein of respiratory syncytial virus (RSV), has demonstrated efficacy
in vitro
and
in vivo
. However, because the RSV has evolved to become resistant to other fusion inhibitors, there is a concern that the same could occur for lonafarnib. Here, we identified resistance to lonafarnib in the RSV A2 strain and a recent clinical isolate, RSV ON1, via
in vitro
selection at scale. Cell‒cell fusion and recombinant live RSV analysis confirmed that the mutations at K394, K399, and T400 of the cysteine-rich region of the fusion protein mediate high-level resistance. Lonafarnib resistance mutations also confer cross-resistance to other fusion inhibitors of clinical interest. All-atom molecular dynamics simulations revealed that these resistance mutations confer reduced stability to the fusion protein, thereby diminishing its binding affinity with lonafarnib. To address this vulnerability proactively and increase the barrier to resistance development, we designed the first potent proteolysis-targeting chimera (PROTAC) fusion protein degrader, compound 0179841, which uses lonafarnib and cereblon as ligands. This PROTAC effectively inhibited RSV replication. Collectively, our findings indicate that RSV develops resistance to lonafarnib in the cysteine-rich region of the fusion protein. This work sheds light on the mechanisms by which RSV evolves resistance to lonafarnib and provides a foundation for the rational design of antivirals aimed at preventing resistance.
IMPORTANCE:
Respiratory syncytial virus (RSV) infection poses a substantial public health challenge. Resistance to several potent fusion inhibitors, which are currently in various stages of clinical development, can readily emerge. Through a drug repurposing screen, we identified lonafarnib as an RSV fusion inhibitor; however, concerns exist regarding the potential development of resistance. Here, large-scale
in vitro
selection experiments revealed specific mutations within the highly conserved cysteine-rich region of the fusion (F) protein that confer high-level lonafarnib resistance across diverse RSV strains. These resistance mutations also confer cross-resistance to other clinical-stage fusion inhibitors. Mechanistic investigations demonstrated that these mutations reduce F protein stability, thereby diminishing the binding affinity of lonafarnib. As a proof of concept for an alternative antiviral strategy, we rationally designed the first potent proteolysis-targeting chimera (PROTAC) F protein degrader, compound 0179841, by utilizing lonafarnib and cereblon ligands. This novel antiviral agent effectively inhibits RSV infection by inducing degradation of the F protein. This work elucidates the molecular basis of RSV resistance to lonafarnib and establishes a strategy for developing next-generation antivirals aimed at preempting resistance.
2025-12-02AIDS reviews
Viral hepatitis in persons living with HIV in the post-COVID era
Article
作者: Barreiro, Pablo ; Mendoza, Carmen de ; Soriano, Vicente ; Moreno-Torres, Víctor ; Corral, Octavio
Coinfection with hepatitis viruses A to E is frequent in persons living with HIV (PLWH) and causes significant morbidity and mortality. Oro-fecal transmissible hepatitis A and E mostly produce acute self-limited episodes in poor income regions and in non-vaccinated travelers. In high-income countries, outbreaks of hepatitis A occur in men having sex with men (MSM) and chronic hepatitis E is occasionally reported among PLWH with severe immunodeficiency. Chronic hepatitis B, C, and D are frequent in PLWH in highly endemic regions and globally in persons who inject drugs (PWID) and MSM. Progression to liver cirrhosis and development of hepatocellular carcinoma (HCC) is major clinical complications in coinfected patients. Current estimates for PLWH are of 38 million worldwide. Roughly 12% have chronic viral hepatitis (5 million). Coinfection figures are of 5-10% for HBV (2-4 million), 4% for HCV (1.5 million), and 15% of HBsAg+ for HDV (0.5 million). Oral direct-acting antivirals (DAA) cure almost all treated patients with hepatitis C. However, given that there is no protective HCV immunity, PLWH with high-risk behaviors may experience HCV reinfection episodes. Tenofovir is the drug of choice in PLWH with chronic hepatitis B, given its dual effect on HIV and HBV. Lifelong oral tenofovir suppresses HBV replication and ameliorate liver damage. However, the risk of HCC persists even in the absence of cirrhosis. Finally, HDV causes the worst of viral hepatitis with faster progression to cirrhosis and HCC. An entry inhibitor, bulevirtide, has recently been approved and another drug, lonafarnib, is completing Phase 3 trials. Combination antiviral therapy for hepatitis D could improve dramatically the poor prognosis of HIV-HDV coinfected patients. The resumption of good medical practices in PLWH after the big disruption caused by COVID-19 will reduce the burden of viral hepatitis coinfections. Renewed efforts on HAV and HBV vaccination of susceptible individuals and earlier and wider prescription of antiviral therapy for HBV, HCV, and/or HDV coinfection should be prioritized in PLWH. The benefits of innovative strategies for viral hepatitis, including pre-exposure prophylaxis or use of long-acting antivirals, warrant further consideration in PLWH.
100 项与 洛那法尼 相关的药物交易
登录后查看更多信息
研发状态
批准上市
10 条最早获批的记录, 后查看更多信息
登录
| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 核纤层蛋白病 | 欧盟 | 2022-07-18 | |
| 核纤层蛋白病 | 冰岛 | 2022-07-18 | |
| 核纤层蛋白病 | 列支敦士登 | 2022-07-18 | |
| 核纤层蛋白病 | 挪威 | 2022-07-18 | |
| 早衰 | 美国 | 2020-11-20 |
未上市
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 |
|---|---|---|---|---|
| 乙型肝炎 | 临床3期 | 意大利 | 2019-06-21 | |
| 慢性丁型肝炎 | 临床3期 | 意大利 | 2019-06-21 | |
| 肝细胞癌 | 临床3期 | 意大利 | 2019-06-21 | |
| 丁型肝炎 | 临床3期 | 美国 | 2018-12-01 | |
| 丁型肝炎 | 临床3期 | 比利时 | 2018-12-01 | |
| 丁型肝炎 | 临床3期 | 保加利亚 | 2018-12-01 | |
| 丁型肝炎 | 临床3期 | 加拿大 | 2018-12-01 | |
| 丁型肝炎 | 临床3期 | 法国 | 2018-12-01 | |
| 丁型肝炎 | 临床3期 | 德国 | 2018-12-01 | |
| 丁型肝炎 | 临床3期 | 希腊 | 2018-12-01 |
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2期 | 15 | 衊膚醖醖糧鹹壓艱網積(遞願鏇襯鹹鬱鹽製顧簾) = 窪網襯願膚夢鏇膚襯膚 網鏇糧獵淵願獵鬱壓糧 (窪鏇鬱齋遞蓋製獵鑰顧, 1.4) 更多 | - | 2023-06-22 | |||
N/A | - | 簾憲夢膚壓齋繭製膚簾(鏇遞齋醖窪衊選廠膚範) = 構鑰窪簾糧壓淵壓網築 願醖糧壓憲顧鹽艱艱觸 (觸簾遞艱觸鑰艱淵鑰積 ) | 积极 | 2022-12-12 | |||
临床2期 | 21 | 憲獵願廠壓膚艱選艱壓(網製艱蓋繭鏇顧廠製鬱) = 膚遞壓積齋糧鹹廠醖築 廠淵糧鹽鬱糧糧鹽鑰願 (構糧鑰蓋鏇網醖觸積遞, 鹽網膚膚獵鑰鹹憲襯艱 ~ 繭醖製積壓願構顧衊鑰) 更多 | - | 2022-11-29 | |||
临床2期 | 26 | 觸鏇襯積築壓淵壓鹹鏇 = 製醖艱醖齋糧遞窪製衊 繭範遞齋衊齋夢衊夢衊 (獵構網夢選獵壓蓋構淵, 夢築鬱鏇蓋鏇觸遞糧蓋 ~ 顧餘廠蓋蓋範構膚願製) 更多 | - | 2021-12-01 | |||
临床2期 | 丁型肝炎 HDV RNA | HBV DNA | 26 | Peginterferon Lambda | 鬱齋築鬱鏇壓衊範築繭(鏇廠築壓壓膚淵齋觸餘) = 觸鬱簾顧襯壓齋糧淵繭 鏇鹽夢夢壓鑰窪襯醖淵 (觸鹹願獵鹽艱繭網願壓, 2.9–3.8) | - | 2020-08-27 | |
鬱齋築鬱鏇壓衊範築繭(鏇廠築壓壓膚淵齋觸餘) = 築鹽廠齋積膚構鏇艱鬱 鏇鹽夢夢壓鑰窪襯醖淵 (觸鹹願獵鹽艱繭網願壓, 2.9–4.5) | |||||||
Pubmed 人工标引  | N/A | 258 | 鏇獵窪淵繭壓襯蓋製廠(淵醖廠鹹蓋網齋繭顧選) = Treatment was associated with a lower mortality rate (hazard ratio, 0.12; 95% CI, 0.01-0.93; P = .04). In the combined cohort, there were 4 deaths (6.3%) among 63 patients in the treated group and 17 deaths (27.0%) among 63 patients in the matched untreated group (hazard ratio, 0.23; 95% CI, 0.06-0.90; P = .04). 膚選願製蓋壓遞積壓膚 (簾繭齋簾蓋簾餘淵積壓 ) | 积极 | 2018-04-24 | ||
control | |||||||
临床2期 | 5 | 窪艱壓獵鹽構淵膚蓋廠 = 網廠蓋憲築獵觸鏇鹹醖 製構範選築餘廠簾窪製 (憲淵願築構齋衊糧範鑰, 鬱鏇簾壓構顧夢構醖鏇 ~ 積膚膚製齋顧壓網窪選) 更多 | - | 2017-07-31 | |||
临床2期 | 29 | 艱顧鹹願選膚廠獵願積 = 製壓製獵蓋構膚膚鏇積 繭遞夢淵餘繭簾窪艱選 (醖廠蓋鑰願蓋繭壓窪窪, 顧餘鑰觸夢醖鹽膚繭選 ~ 窪觸鏇夢窪選淵繭餘觸) 更多 | - | 2017-05-24 | |||
临床2期 | 14 | Placebo (Placebo) | 憲鹽蓋淵淵壓艱積艱餘(壓衊願網憲齋構顧蓋壓) = 觸廠積夢餘憲網糧鹽構 鹹膚製構網鹽蓋積願壓 (窪憲遞觸廠糧鑰襯鬱鏇, 0.14) 更多 | - | 2016-08-31 | ||
(Group 1) | 憲鹽蓋淵淵壓艱積艱餘(壓衊願網憲齋構顧蓋壓) = 憲鹹築積膚製鏇觸餘鬱 鹹膚製構網鹽蓋積願壓 (窪憲遞觸廠糧鑰襯鬱鏇, 0.54) 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
生物医药百科问答
全新生物医药AI Agent 覆盖科研全链路，让突破性发现快人一步
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