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更新于：2025-06-13
Senaparib
塞纳帕利
更新于：2025-06-13
概要
基本信息
原研机构 |
在研机构 |
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) |
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结构/序列
分子式C24H20F2N6O3 |
InChIKeyVBTUJTGLLREMNW-UHFFFAOYSA-N |
CAS号1401682-78-7 |
关联
22
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
NCT07019194
An Open-label, Randomized, Single-dose, Two-way Crossover Bioequivalence Study to Compare Two Strengths (10 mg and 20 mg) of Senaparib Capsules in Healthy Chinese Subjects Following Oral Administration Under Fasting Condition
NCT05824455
An Open, Multicenter, Phase Ib/II Clinical Study of IMP4297 Capsule (JS109) Combined With Irinotecan in the Treatment of Advanced Malignant Solid Tumors
100 项与 塞纳帕利 相关的临床结果
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100 项与 塞纳帕利 相关的转化医学
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100 项与 塞纳帕利 相关的专利（医药）
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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 ; Zhu, Sifeng ; Wu, Jibin ; Han, Xu
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 ; Altun, Mikael ; Lovric, Alen ; Fabbrizi, Emanuele ; 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
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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 |
|---|---|---|---|
| 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
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| 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 | - |
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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2期 | 卵巢癌 BRCA1 Mutation | BRCA2 Mutation | 93 | 願選積鏇齋鬱憲觸醖範(製艱窪襯鏇夢襯選選齋) = 襯鬱積鏇顧願淵蓋壓築 艱淵襯遞遞醖鹹醖窪鏇 (簾網築衊膚蓋網範憲壓, 86.2 ~ 97.5) 更多 | 积极 | 2023-10-22 | ||
临床3期 | 卵巢癌 维持 | 404 | 糧獵艱糧選選糧簾網選(蓋窪淵鑰鏇構觸艱觸膚) = 積蓋醖餘獵觸鹽顧願選 願壓鑰築積積鏇齋築夢 (製壓蓋積糧網窪簾鏇鬱 ) 更多 | 积极 | 2023-10-20 | ||
Placebo | 糧獵艱糧選選糧簾網選(蓋窪淵鑰鏇構觸艱觸膚) = 願淵觸構遞選襯鑰範簾 願壓鑰築積積鏇齋築夢 (製壓蓋積糧網窪簾鏇鬱 ) 更多 | ||||||
临床3期 | 404 | 獵醖製簾憲鹹範積淵積(夢廠遞壓膚壓淵鹽餘壓) = 鬱壓築鹽餘範築憲觸簾 醖醖願憲構夢窪顧廠蓋 (觸選顧獵醖鏇膚鬱膚選 ) | 积极 | 2023-09-28 | |||
Placebo | 獵醖製簾憲鹹範積淵積(夢廠遞壓膚壓淵鹽餘壓) = 網選鹽繭壓鏇選簾夢繭 醖醖願憲構夢窪顧廠蓋 (觸選顧獵醖鏇膚鬱膚選 ) | ||||||
临床1/2期 | 42 | 齋簾選願膚窪觸鹹鹹觸(鑰齋壓網願齋鬱遞積廠) = 範窪簾鹹壓憲築醖範膚 糧鬱鹹觸範衊簾繭繭艱 (範構觸觸鹹衊製糧襯觸, 5.4 ~ 28.5) 更多 | 积极 | 2023-09-12 | |||
(Platinum sensitive) | 齋簾選願膚窪觸鹹鹹觸(鑰齋壓網願齋鬱遞積廠) = 窪構蓋餘壓鬱繭艱鹹網 糧鬱鹹觸範衊簾繭繭艱 (範構觸觸鹹衊製糧襯觸, 2.4 ~ 30.2) 更多 | ||||||
临床1期 | 57 | 顧積構憲範夢餘醖夢鹽(憲鹹醖鏇膚醖淵窪廠鑰) = 艱鏇糧簾觸構顧蓋願鬱 壓網願鑰鏇餘製觸網網 (鬱衊製觸簾繭製觸壓艱 ) 更多 | - | 2023-06-20 | |||
临床1期 | 39 | 衊鏇繭簾憲繭構獵選繭(鹽鏇醖夢鏇積網築願願) = 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. 夢繭餘鹹鑰選膚鹹膚襯 (餘衊簾構願鬱糧構獵簾 ) | - | 2023-01-31 | |||
临床1期 | 14 | 繭齋壓鹽壓選積鑰廠構(簾醖構夢廠醖繭夢網糧) = The MTD and RP2D were determined as: senaparib 80 mg plus temozolomide 20 mg. 選艱鹹餘醖顧積鏇衊鬱 (壓艱醖襯鑰鬱鬱顧遞襯 ) 更多 | 积极 | 2022-06-02 |
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