预约演示
更新于：2025-06-04
Senaparib
塞纳帕利
更新于：2025-06-04
概要
基本信息
原研机构 |
非在研机构 |
权益机构 |
最高研发阶段批准上市 |
最高研发阶段(中国)批准上市 |
特殊审评孤儿药 (美国) |
登录后查看时间轴
结构/序列
分子式C24H20F2N6O3 |
InChIKeyVBTUJTGLLREMNW-UHFFFAOYSA-N |
CAS号1401682-78-7 |
关联
21
项与 塞纳帕利 相关的临床试验NCT06617923
A Phase 2 Study of Senaparib in Combination With Temozolomide in ARID1A Mutation Associated Ovarian Cancer
NCT05824455
An Open, Multicenter, Phase Ib/II Clinical Study of IMP4297 Capsule (JS109) Combined With Irinotecan in the Treatment of Advanced Malignant Solid Tumors
CTR20221034
一项开放、随机、单剂量、二交叉、比较中国健康受试者在空腹状态下IMP4297胶囊两种规格（10 mg和20 mg）的生物等效性研究
100 项与 塞纳帕利 相关的临床结果
登录后查看更多信息
100 项与 塞纳帕利 相关的转化医学
登录后查看更多信息
100 项与 塞纳帕利 相关的专利（医药）
登录后查看更多信息
10
项与 塞纳帕利 相关的文献（医药）2025-05-01JOURNAL OF CONTROLLED RELEASE
Multifunctional nanoparticle-mediated targeting of metabolic reprogramming and DNA damage response pathways to treat drug-resistant triple-negative breast cancer
Article
作者: Wang, Jue ; Wang, Cheng ; Cai, Zimin ; Sun, Chao ; Han, Xu ; Zhu, Sifeng ; Wu, Jibin
Multi-drug resistance and immunosuppressive triple-negative breast cancer (TNBC) is triggered by the Warburg effect, which promotes homologous recombination repair (HRR) and upregulates expression of P-glycoprotein (P-gp), in turn preventing DNA damage from chemotherapy and creating an immunosuppressive microenvironment. It is therefore of clinical relevance to develop an effective delivery system that targets metabolic reprogramming and DNA damage response pathways for the treatment of drug-resistant TNBC. Herein, a P-gp-inhibiting and GSH-responsive multifunctional drug carrier targeting integrin αvβ3 was synthesised for the delivery of Lonidamine-prodrug (M1, glycolysis inhibitor) and Senaparib (Se, Poly [ADP-ribose] polymerase inhibitor). The nanodrug delivery system (iPR@M1/Se nanoparticles) exhibit effective tumour penetration and P-gp inhibition, effectively inducing DNA damage and apoptosis in Olaparib-resistant TNBC cells in vitro, as well as a higher tumour inhibitory rate compared with that of Se (81.82 % ± 2.31 % vs 43.91 % ± 4.65 %) in vivo. Mechanistically, iPR@M1/Se nanoparticles not only reshaped the immunosuppressive microenvironment resulting from tumour glycolysis, but also downregulated the expression of HRR-related protein, fostering the cytoplasmic accumulation of DNA damage fragments, which induced activation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon gene (STING) pathway. Experimental results show that iPR@M1/Se nanoparticles effectively promote dendritic cell maturation and T lymphocyte activation, which elicits long-term immune memory responses, and prevents tumour recurrence and lung metastasis. Therefore, these multifunctional nanoparticles have great potential and provide a clinically relevant and valuable option for Olaparib-resistant TNBC.
2025-04-01JOURNAL OF BIOLOGICAL CHEMISTRY
Duplexed CeTEAM drug biosensors reveal determinants of PARP inhibitor selectivity in cells
Article
作者: Alam, Seher ; Rotili, Dante ; Lovric, Alen ; Fabbrizi, Emanuele ; Altun, Mikael ; Pires, Maria J ; Valerie, Nicholas C K
Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) targeting PARP1 and PARP2 have revolutionized cancer therapy by selectively killing cancer cells with defective DNA repair. However, achieving PARP1 or PARP2-selective inhibitors is difficult due to structural homology. Selectivity profiling is typically done with purified proteins, but these lack the complexity of intracellular environments and could therefore be inaccurate. Here, we duplex PARP1 L713F-GFP and PARP2 L269A-mCherry cellular target engagement by accumulation of mutant (CeTEAM) drug biosensors to systematically characterize binding and cell cycle alterations of 27 PARPi. Our results reveal that most PARPi are equipotent for both PARPs, including the next-generation drug, senaparib. However, benzimidazole carboxamide (niraparib) derivatives demonstrated PARP1-selective tendencies, while phthalazinones (olaparib) favored PARP2. AZD5305, a reported PARP1-selective inhibitor with characteristics of both series, was the exception and appears ∼1600-fold more potent toward PARP1. In agreement with current understanding, we see that trapping-associated S/G2-phase transitions positively correlate with PARP1/2 binding potency, while some potent binders, such as veliparib, did not - likely reflecting their allosteric influence on DNA retention. We also assessed the effect of the PARP1/2 active site component, histone PARylation factor 1, on intracellular PARPi binding and see that its depletion elicits slight deviations in apparent binding potency, while contributing additively to trapping-like phenotypes. The PARP1/2 CeTEAM platform thus provides a structural roadmap for the development of selective PARPi and should facilitate the discovery of targeted therapies. Furthermore, our results highlight that multiplexing CeTEAM biosensors and layered genetic perturbations can systematically profile determinants of intracellular drug selectivity.
2025-01-02MOLECULAR CANCER THERAPEUTICS
The Discovery of a Potent PARP1 Inhibitor Senaparib
Article
作者: Guo, Mingchuan ; Cai, Sui X. ; Tian, Ye E. ; Jiang, Yangzhen ; Ma, Ning ; Wang, Xiaozhu
Abstract:
PARP1 is a critical enzyme involved in DNA damage repair. It belongs to a superfamily of proteins and catalyzes poly(ADP-ribosyl)ation (PARylation). PARP1 inhibitors are effective to treat tumors that have homologous recombination deficiency such as those with BRCA1/2 mutations. The PARP1 inhibitors that have been approved by FDA inhibit both PARP1 and PARP2. PARP2 has also been suggested to play a similar function in DNA repair as PARP1. In addition to inhibiting PARP1 enzymatic activities, PARP1 inhibitors cause the PARP1 enzyme to be “trapped” on DNA, stalling the DNA replication fork and eventually causing double-strand DNA breaks and cell death. Here, we report a PARP1 inhibitor, Senaparib, which has a novel chemical structure and high potency inhibiting PARP1/2 enzymes. Senaparib was highly potent in cell viability tests against tumor cells with BRCA1/2 mutations. It was efficacious in cell line-derived and patient-derived xenograft models in tumors harboring BRCA1/2 mutations. In combination studies, Senaparib used with temozolomide had shown strong synergistic cytotoxicity in both in vitro and in vivo experiments. Senaparib represents a novel class of PARP1 inhibitors that can be used for the treatment of cancer. A phase III clinical study of Senaparib for maintenance treatment following first-line chemotherapy in patients with advanced ovarian cancer has met its primary endpoint, and a new drug application of Senaparib has been accepted by the National Medical Products Administration of China for review.
110
项与 塞纳帕利 相关的新闻（医药）2025-05-30
·英派药业
ASCO会议临床结果临床1期AACR会议
2025-04-30
·英派药业
AACR会议临床2期临床结果临床1期
2025-04-02
·药事纵横
上市批准申请上市
100 项与 塞纳帕利 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 |
|---|---|---|---|
| 输卵管癌 | 中国 | 2025-01-14 | |
| 卵巢上皮癌 | 中国 | 2025-01-14 | |
| 原发性腹膜癌 | 中国 | 2025-01-14 |
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 |
|---|---|---|---|---|
| 转移性去势抵抗性前列腺癌 | 临床2期 | 美国 | 2021-12-31 | |
| 转移性去势抵抗性前列腺癌 | 临床2期 | 中国 | 2021-12-31 | |
| 转移性去势抵抗性前列腺癌 | 临床2期 | 澳大利亚 | 2021-12-31 | |
| 晚期恶性实体瘤 | 临床2期 | 美国 | 2021-09-28 | |
| 晚期恶性实体瘤 | 临床2期 | 澳大利亚 | 2021-09-28 | |
| 晚期恶性实体瘤 | 临床2期 | 韩国 | 2021-09-28 | |
| 广泛期小细胞肺癌 | 临床2期 | 美国 | 2021-09-28 | |
| 广泛期小细胞肺癌 | 临床2期 | 澳大利亚 | 2021-09-28 | |
| 广泛期小细胞肺癌 | 临床2期 | 韩国 | 2021-09-28 | |
| 小细胞肺癌 | 临床2期 | 中国 | - |
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 | 卵巢癌 BRCA1 Mutation | BRCA2 Mutation | 93 | 繭願製鏇蓋襯繭觸繭網(築鬱夢鏇糧願壓淵齋淵) = 遞鹽窪糧餘醖遞遞壓鬱 齋夢鏇鑰顧積夢鹽夢製 (壓顧築鏇獵襯醖醖願廠, 86.2 ~ 97.5) 更多 | 积极 | 2023-10-22 | ||
临床3期 | 卵巢癌 维持 | 404 | 醖襯遞鏇顧廠膚壓壓壓(淵顧顧鑰鏇顧積廠艱醖) = 艱糧簾範繭鑰壓窪衊觸 壓壓鬱憲淵顧齋廠夢醖 (願積醖觸齋夢衊繭獵廠 ) 更多 | 积极 | 2023-10-20 | ||
Placebo | 醖襯遞鏇顧廠膚壓壓壓(淵顧顧鑰鏇顧積廠艱醖) = 壓襯範鹹廠願製構廠憲 壓壓鬱憲淵顧齋廠夢醖 (願積醖觸齋夢衊繭獵廠 ) 更多 | ||||||
临床3期 | 404 | 鹹蓋糧齋鑰憲鏇壓網餘(鬱醖齋觸鹽衊網築淵夢) = 選夢繭繭鏇衊鑰餘構夢 獵願顧糧齋鏇艱襯襯觸 (淵製獵顧襯夢繭範壓製 ) | 积极 | 2023-09-28 | |||
Placebo | 鹹蓋糧齋鑰憲鏇壓網餘(鬱醖齋觸鹽衊網築淵夢) = 製蓋顧蓋遞獵網淵鏇夢 獵願顧糧齋鏇艱襯襯觸 (淵製獵顧襯夢繭範壓製 ) | ||||||
临床1/2期 | 42 | 選製範簾獵範鬱夢鑰襯(遞鏇獵夢糧選艱簾積顧) = 觸網憲積鏇糧製艱鬱艱 淵網遞積蓋鑰觸醖鬱觸 (淵廠範艱衊淵壓糧觸範, 5.4 ~ 28.5) 更多 | 积极 | 2023-09-12 | |||
(Platinum sensitive) | 選製範簾獵範鬱夢鑰襯(遞鏇獵夢糧選艱簾積顧) = 鏇鏇衊衊鬱範選簾艱糧 淵網遞積蓋鑰觸醖鬱觸 (淵廠範艱衊淵壓糧觸範, 2.4 ~ 30.2) 更多 | ||||||
临床1期 | 57 | 淵糧鹹餘膚鹹蓋鑰艱願(鏇簾顧餘醖鹽艱繭範艱) = 顧膚夢淵積願鏇壓夢窪 觸構夢構夢願獵蓋齋餘 (獵憲構積觸積鏇繭廠膚 ) 更多 | - | 2023-06-20 | |||
临床1期 | 39 | 製膚齋齋網艱構鹹網夢(獵襯艱壓鬱夢獵簾遞鏇) = Most treatment-emergent adverse events were grade 1-2 (91%). Seven patients (17.9%) reported hematologic treatment-emergent adverse events. Treatment-related adverse events occurred in eight patients (20.5%), and the most frequent was nausea (7.7%). Two deaths were reported after the end of study treatment, one of which was considered a complication from senaparib-related bone marrow failure. 構夢網顧膚夢築鑰鏇遞 (願膚衊網蓋範鏇齋簾遞 ) | - | 2023-01-31 | |||
临床1期 | 14 | 選憲網觸選積衊窪夢構(鹹襯齋糧齋醖鹹醖鏇鹹) = The MTD and RP2D were determined as: senaparib 80 mg plus temozolomide 20 mg. 糧願築獵壓積願窪壓鬱 (壓襯憲鑰夢窪壓築鬱獵 ) 更多 | 积极 | 2022-06-02 |
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
Eureka LS:
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