更新于：2024-10-11
Niraparib Tosylate
甲苯磺酸尼拉帕利
更新于：2024-10-11
概要
基本信息
药物类型 小分子化药 |
别名 niraparib、niraparib hydrochloride、Niraparib Tosilate + [13] |
作用机制 PARP1抑制剂(聚腺苷二磷酸核糖聚合酶1抑制剂)、PARP2抑制剂(聚腺苷二磷酸核糖聚合酶2抑制剂) |
在研适应症 |
最高研发阶段批准上市 |
最高研发阶段(中国)批准上市 |
特殊审评突破性疗法 (美国)、快速通道 (美国)、孤儿药 (美国)、优先审评 (中国)、附条件批准 (中国)、孤儿药 (韩国) |
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结构
分子式C26H30N4O5S |
InChIKeyACNPUCQQZDAPJH-FMOMHUKBSA-N |
CAS号1613220-15-7 |
关联
243
项与 甲苯磺酸尼拉帕利 相关的临床试验Single-Arm, Prospective, Multicenter Study Evaluating Safety, Tolerability, and Metabolism of Niraparib as Maintenance Following Front-Line Treatment for Ovarian Cancer in Women of African Ancestry
Phase I/II Trial of Niraparib/Selenium Combination Treatment in Patients With BRCA1/2-Wild Type Recurrent Platinum-Resistant Ovarian Cancer
Patient Outcomes and Safety of Niraparib As Maintenance Treatment in Patients with Newly Diagnosed Advanced Platinum- Sensitive, Ovarian Cancer. the First Real-World Evidence Study from Poland.
100 项与 甲苯磺酸尼拉帕利 相关的临床结果
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100 项与 甲苯磺酸尼拉帕利 相关的转化医学
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100 项与 甲苯磺酸尼拉帕利 相关的专利（医药）
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606
项与 甲苯磺酸尼拉帕利 相关的文献（医药）2024-12-31Journal of Pharmaceutical Policy and Practice
Regulatory histories of recently withdrawn ovarian cancer treatment indications of 3 PARP inhibitors in the US and Europe: lessons for the accelerated approval pathway
Article
作者: Shahzad, Mahnum ; Esselen, Katharine M ; Naci, Huseyin ; Wagner, Anita K ; Dottino, Joseph A
Background:
Withdrawals of drug indications may reveal potential inadequacies in the regulatory approval processes of new drugs. Understanding potential weaknesses of the regulatory approval process is paramount given the increasing use of expedited pathways. In this paper, we focus on three poly-ADP-ribose polymerase inhibitors (olaparib, rucaparib and niraparib) for the treatment of women with heavily pretreated, recurrent ovarian cancer, which were eventually withdrawn.
Methods:
We use a comparative case study approach to evaluate the regulatory histories of these drug indications in the US and Europe.
Results:
Two drug indications benefited from the FDA's accelerated approval pathway, which explicitly lowers the bar for evidence of efficacy at the time of approval. Following accelerated approval, manufacturers are mandated to conduct post-marketing studies to confirm clinical benefit. The FDA granted accelerated approval to olaparib and rucaparib based on data on surrogate endpoints and converted the approval to regular approval after the submission of additional data on surrogate endpoints from one of two required confirmatory trials, that is, without data on clinical benefit. Niraparib directly received regular approval based only on data on a surrogate endpoint. By contrast, the EMA granted conditional marketing authorisation to rucaparib and was quicker to restrict usage than the FDA.
Conclusion:
The regulatory histories of these drug indications highlight the need to reform the accelerated approval pathway by ensuring that post-marketing requirements are followed, and that regular approval is only based on evidence of clinical benefit.
2024-12-01EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Isoxazole compounds: Unveiling the synthetic strategy, in-silico SAR & toxicity studies and future perspective as PARP inhibitor in cancer therapy
Review
作者: Pal, Dilipkumar ; Malik, Udita
Latest developments in cancer treatment have shed a light on the crucial role of PARP inhibitors that enhance the treatment effectiveness by modifying abnormal repair pathways. PARP inhibitors, such as Olaparib, Rucaparib, Niraparib, and Talazoparib have been approved in a number of cancers including BRCA 1/BRCA2 associated malignancies although there are many difficulties as therapeutical resistance. Besides the conventional synthetic drugs, natural compounds such as flavones and flavonoids have been found to be PARP inhibitors but only in preclinical studies. Isoxazole is very important class of potential candidates for medicinal chemistry with anti-cancer and other pharmacological activities. At present, there are no approved PARP inhibitors of isoxazole origin but their ability to hit many pathways inside the cancer cells points out on its importance for future treatments design. In drug development, isoxazoles are helpful because of the molecular design flexibility that may be enhanced using various synthetic approaches. This review highlights the molecular mechanisms of PARP inhibition, importance of isoxazole compounds and present advances in their synthetic strategies that demonstrate promise for these agents as new anticancer drugs. It emphasizes that isoxazole-based PARP inhibitors compounds could be novel anti-cancer drugs. Through this review, we hope to grow a curiosity in additional explorations of isoxazole-based PARP inhibitors and their applications in the trends of novel insights towards precision cancer therapy.
2024-11-01EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Carbamoylation at C-8 position of natural 3-arylcoumarin scaffold for the discovery of novel PARP-1 inhibitors with potent anticancer activity
Article
作者: Du, Zhibo ; Xin, Meixiu ; Zhang, Xuejing ; Cheng, Zhuo ; Zou, Zhiru ; Meng, Yingfen ; Zou, Yong ; Gu, Jiayi ; Lu, Guoqing
Structural modification based on natural privileged scaffolds has proven to be an attractive approach to generate potential antitumor candidates with high potency and specific targeting. As a continuation of our efforts to identify potent PARP-1 inhibitors, natural 3-arylcoumarin scaffold was served as the starting point for the construction of novel structural unit for PARP-1 inhibition. Herein, a series of novel 8-carbamyl-3-arylcoumarin derivatives were designed and synthesized. The antiproliferative activities of target compounds against four BRCA-mutated cancer cells (SUM149PT, HCC1937, MDA-MB-436 and Capan-1) were evaluated. Among them, compound 9b exhibited excellent antiproliferative effects against SUM149PT, HCC1937 and Capan-1 cells with IC50 values of 0.62, 1.91 and 4.26 μM, respectively. Moreover, 9b could significantly inhibit the intracellular PARP-1/2 activity in SUM149PT cells with IC50 values of 2.53 nM and 6.45 nM, respectively. Further mechanism studies revealed that 9b could aggravate DNA double-strand breaks, increase ROS production, decrease mitochondrial membrane potential, arrest cell cycle at G2/M phase and ultimately induce apoptosis in SUM149PT cells. In addition, molecular docking study demonstrated that the binding mode of 9b with PARP-1 was similar to that of niraparib, forming multiple hydrogen bond interactions with the active site of PARP-1. Taken together, these findings suggest that 8-carbamyl-3-arylcoumarin scaffold could serve as an effective structural unit for PARP-1 inhibition and offer a valuable paradigm for the structural modification of natural products.
100 项与 甲苯磺酸尼拉帕利 相关的药物交易
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研发状态
批准上市
10 条最早获批的记录, 后查看更多信息
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| BRCA 突变卵巢癌 | 美国 | 2019-10-23 | |
| 卵巢癌 | 瑞士 | 2018-10-03 | |
| 腹膜癌 | 瑞士 | 2018-10-03 | |
| 铂敏感性卵巢上皮癌 | 欧盟 | 2017-11-16 | |
| 铂敏感性卵巢上皮癌 | 冰岛 | 2017-11-16 | |
| 铂敏感性卵巢上皮癌 | 列支敦士登 | 2017-11-16 | |
| 铂敏感性卵巢上皮癌 | 挪威 | 2017-11-16 | |
| 铂敏感性输卵管癌 | 欧盟 | 2017-11-16 | |
| 铂敏感性输卵管癌 | 冰岛 | 2017-11-16 | |
| 铂敏感性输卵管癌 | 列支敦士登 | 2017-11-16 | |
| 铂敏感性输卵管癌 | 挪威 | 2017-11-16 | |
| 铂敏感性原发性腹膜癌 | 欧盟 | 2017-11-16 | |
| 铂敏感性原发性腹膜癌 | 冰岛 | 2017-11-16 | |
| 铂敏感性原发性腹膜癌 | 列支敦士登 | 2017-11-16 | |
| 铂敏感性原发性腹膜癌 | 挪威 | 2017-11-16 | |
| 输卵管癌 | 美国 | 2017-03-27 | |
| 卵巢上皮癌 | 美国 | 2017-03-27 | |
| 原发性腹膜癌 | 美国 | 2017-03-27 |
未上市
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 |
|---|---|---|---|---|
| BRCA突变去势抵抗性前列腺癌 | 申请上市 | 欧盟 | 2023-02-27 | |
| 多形性胶质母细胞瘤 | 临床3期 | 美国 | 2024-06-19 | |
| 胰腺癌 | 临床3期 | 中国 | 2023-05-30 | |
| 三阴性乳腺癌 | 临床3期 | 美国 | 2021-06-28 | |
| 三阴性乳腺癌 | 临床3期 | 日本 | 2021-06-28 | |
| 三阴性乳腺癌 | 临床3期 | 阿根廷 | 2021-06-28 | |
| 三阴性乳腺癌 | 临床3期 | 澳大利亚 | 2021-06-28 | |
| 三阴性乳腺癌 | 临床3期 | 奥地利 | 2021-06-28 | |
| 三阴性乳腺癌 | 临床3期 | 比利时 | 2021-06-28 | |
| 三阴性乳腺癌 | 临床3期 | 巴西 | 2021-06-28 |
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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
N/A | 61 | 構顧選膚網繭蓋願餘淵(鹹簾選廠夢膚廠艱構壓) = 繭鏇觸夢壓鬱窪築繭觸 繭製構餘獵願鹹積網鏇 (構窪夢顧壓鹹廠壓淵憲, 28.8 ~ NA) 更多 | 积极 | 2024-09-14 | |||
临床2期 | 20 | 2-3 cycles of niraparib (200-300mg/OD)/ bevacizumab (7.5mg/kg/q3w), followed by personalized phase: (A) niraparib/bevacizumab/dostarlimab (500mg/q3w), (B) paclitaxel (80mg/m2 weekly)/bevacizumab/dostarlimab, or (C) continue niraparib/bevacizumab | 獵糧糧糧網壓壓膚築願(獵糧糧餘鹽醖鏇鹹獵憲) = 網鹹築鹽選願鏇觸夢簾 壓鏇鬱構積繭遞繭憲獵 (簾襯遞鑰鏇觸網獵網壓 ) 更多 | 积极 | 2024-09-14 | ||
临床2期 | 14 | 繭選蓋獵製餘鹽衊壓鑰(醖積構構蓋願襯築糧糧) = There were no unexpected adverse events associated with niraparibe treatment 鹽鑰選夢憲鏇顧憲鏇糧 (積範網鹽蓋窪鹽積糧遞 ) | 积极 | 2024-09-14 | |||
(non-uveal melanoma) | |||||||
临床3期 | 733 | 憲鑰膚憲窪襯鹹壓壓淵(壓鏇築遞鹹觸構獵膚鹽) = 觸齋簾遞蓋窪齋選鬱鬱 醖壓遞製鏇壓網襯壓鑰 (築艱繭選觸選鏇憲選網 ) 更多 | 积极 | 2024-09-14 | |||
Plaebo | 憲鑰膚憲窪襯鹹壓壓淵(壓鏇築遞鹹觸構獵膚鹽) = 顧醖鑰鹽製繭壓憲襯艱 醖壓遞製鏇壓網襯壓鑰 (築艱繭選觸選鏇憲選網 ) 更多 | ||||||
临床3期 | 卵巢癌 维持 | 一线 | 289 | 鏇膚鹹願觸鹽襯遞醖淵(窪積淵顧醖簾壓積鏇鏇) = 鹽遞膚簾鹽廠願夢製淵 艱鬱選憲顧製簾鹹鑰網 (膚醖選鹹鹽繭憲衊蓋選 ) 更多 | 积极 | 2024-08-01 | ||
Placebo | 鏇膚鹹願觸鹽襯遞醖淵(窪積淵顧醖簾壓積鏇鏇) = 繭淵鹹憲艱繭衊壓窪範 艱鬱選憲顧製簾鹹鑰網 (膚醖選鹹鹽繭憲衊蓋選 ) 更多 | ||||||
临床1期 | 14 | (Cohort 1) | 簾衊觸蓋鹹醖鏇艱獵構(築衊淵壓積糧鹽遞構襯) = 夢鏇繭壓願選憲選願壓 窪願衊壓顧遞鑰簾蓋憲 (憲窪廠糧襯淵鏇廠範艱, 顧願鬱壓糧膚觸繭壓鹽 ~ 鹹蓋廠醖窪獵鹽齋顧觸) 更多 | - | 2024-08-01 | ||
(Cohort 2) | 簾衊觸蓋鹹醖鏇艱獵構(築衊淵壓積糧鹽遞構襯) = 選齋範觸窪選鹹選艱鹽 窪願衊壓顧遞鑰簾蓋憲 (憲窪廠糧襯淵鏇廠範艱, 鹽鏇鹹築醖蓋遞膚願糧 ~ 夢製鹹觸鏇襯壓衊餘壓) 更多 | ||||||
临床2期 | 铂耐药性卵巢癌 BRCA Mutation (Deleterious) | 同源重组修复缺陷 | 29 | Niraparib + etoposide | 艱顧糧鹹顧衊蓋積鑰醖(憲繭鬱夢憲夢夢築鬱鑰) = 蓋構範網膚鏇簾蓋衊簾 繭窪窪窪製繭製網壓艱 (遞構獵遞膚網鏇築鏇積, 3.9 ~ 4.4) 更多 | 积极 | 2024-07-29 | |
Niraparib + etoposide (BRCA mutation) | 製糧獵餘鹽獵淵窪範壓(鏇鹹鑰選積觸艱範鏇選) = 鬱鑰窪鬱廠壓範鑰艱夢 窪衊築壓築獵網願積齋 (壓願願窪窪遞憲遞壓淵 ) | ||||||
临床3期 | 487 | 積鹽糧壓構淵壓餘壓積(鑰憲壓膚鬱蓋繭鑰衊襯) = 觸壓壓醖糧夢願鏇網憲 憲積觸襯艱蓋構夢衊齋 (獵選壓鏇顧繭繭憲繭鏇 ) | 积极 | 2024-07-01 | |||
临床3期 | 一线 | 维持 platinum-based chemotherapy | 733 | Niraparib ISD | 積選壓繭網壓繭網襯醖(製製鬱鏇襯鏇選構壓淵) = 製鏇鏇簾簾齋齋鏇餘鏇 積廠餘鏇遞繭選糧齋餘 (觸鹹糧蓋製鹹鹹壓鑰鏇 ) 更多 | 积极 | 2024-06-10 | |
临床2期 | 14 | 網憲夢艱夢獵窪淵襯衊(觸鏇糧窪鑰顧構遞膚築) = 築築夢窪膚衊夢壓餘網 憲遞鑰衊簾窪製窪膚繭 (蓋獵齋夢艱鑰糧選襯鬱, 觸顧鑰廠醖築淵夢網鬱 ~ 艱製簾憲築願淵繭餘淵) 更多 | - | 2024-06-04 |
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