更新于：2024-12-24
Olaparib
奥拉帕利
更新于：2024-12-24
概要
基本信息
药物类型 小分子化药 |
别名 4-(3-{[4-(cyclopropylcarbonyl)piperazin-1-yl]carbonyl}-4-fluorobenzyl)phthalazin-1(2H)-one、Olaparib (JAN/USAN/INN)、奥拉帕尼 + [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)、PARP3抑制剂(聚腺苷二磷酸核糖聚合酶3抑制剂) |
在研适应症 |
原研机构 |
最高研发阶段批准上市 |
首次获批日期 欧盟 (2014-12-16), |
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)、加速批准 (美国)、优先审评 (中国)、附条件批准 (中国)、特殊审批 (中国)、孤儿药 (日本)、优先审评 (澳大利亚)、加速批准 (加拿大)、优先审评 (美国)、孤儿药 (美国) |
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结构
分子式C24H23FN4O3 |
InChIKeyFDLYAMZZIXQODN-UHFFFAOYSA-N |
CAS号763113-22-0 |
关联
510
项与 奥拉帕利 相关的临床试验Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART): Adaptive Clinical Treatment (ACT)
A Phase III Trial of One vs. Two Years of Maintenance Olaparib, With or Without Bevacizumab, in Patients With BRCA1/2 Mutated or Homologous Recombination Deficient (HRD+) Ovarian Cancer Following Response to First Line Platinum Based Chemotherapy
A Randomized Phase II Study of Temozolomide Monotherapy or in Combination With Olaparib in Patients With METHYLATED 06-Methylguanine-DNA Methyltransferase (MGMT) Pre-Treated Triple Negative Breast Cancer (TNBC)
100 项与 奥拉帕利 相关的临床结果
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100 项与 奥拉帕利 相关的转化医学
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100 项与 奥拉帕利 相关的专利（医药）
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2,963
项与 奥拉帕利 相关的文献（医药）2025-12-31ANNALS OF MEDICINE
Haematologic outcomes and associated clinical characteristics among patients receiving Olaparib therapy in the UAE: a retrospective chart review
Article
作者: Akour, Amal ; Ibrahim, Mariam ; Nabil, Said ; Kendakji, Saba ; ZainAlAbdin, Sham ; Aburuz, Salahdein ; Wahba, Lina
BACKGROUND:
Poly ADP ribose polymerase (PARP) inhibitors, such as Olaparib (Lynparza®), are pivotal in treating certain cancers, particularly those linked to BReast CAncer gene (BRCA) mutations. Despite its established efficacy, Olaparib use is associated with various adverse events (AEs), notably haematologic toxicities, such as anaemia. This retrospective chart review study aimed to examine haematologic outcomes and associated factors in patients treated with Olaparib at a tertiary hospital in the UAE.
METHODS:
We reviewed the medical charts of patients prescribed Olaparib and focused on haematologic indices at a baseline of 1-month, 3-month and 6-month follow-up periods. Data were analysed to determine the AEs frequency, transfusions need and potential associated patients' clinical characteristics.
RESULTS:
This study included all patients who received Olaparib (n = 66). Most patients were females (n = 61; 92.4%) and the vast majority were non-smokers (97%) and free of hepatic disease. Themean age of the patients was 57.03-year-old (SD) = 12.06 years), and body mass index (BMI) was 28.16 (SD = 6.40) kg/m2. A high rate of anaemia (70.8%) was detected among the patients during their Olaparib therapy. Approximately, one-third of the patients developed neutropenia and thrombocytopenia. Transfusion was needed in almost half of the patients. Glomerular filtration rate (GFR) and neutropenia were significantly correlated with moderate-severe anaemia (OR = 0.097, 95% CI: 0.011-0.88, p value = .038) and (OR = 9.04, 95% CI: 1.024-79.78, p value = .048), respectively.
CONCLUSIONS:
Our findings highlight the side effects of Olaparib therapy in terms of haematology which could be avoided. Further studies are needed to better understand the therapeutic management of Olaparib and the mitigation of haematologic complications.
2025-03-01CURRENT PHARMACEUTICAL DESIGN
PARP Pioneers: Using BRCA1/2 Mutation-targeted Inhibition to Revolutionize Breast Cancer Treatment
Article
作者: Shah, Kamal ; Bhati, Akash ; Dewangan, Hitesh Kumar ; Aggarwal, Shagun ; Sharma, Navneet
Abstract::
Breast cancer stands on the second position in the world in being common and women happen to
have it with high rate of about five-folds around the world. The causes of occurrence can matter with different
humans be it external factors or the internal genetic ones. Breast cancer is primarily driven by mutations in the
BRCA1 and BRCA2 susceptibility genes. These BC susceptibility genes encode proteins critical for DNA homologous
recombination repair (HRR). Poly (ADP ribose) polymerases (PARP) are the essential enzymes involved
in the repairing of the damaged DNA. So the inhibition of these inhibitors can be considered as the
promising strategy for targeting cancers with defective damage in the deoxyribonucleic acid. Olaparib and talazoparib
are PARP inhibitors (PARPi) are being employed for the monotherapies in case of the deleterious
germline HER2-negative and BRCA-mutated breast cancer. The potency of PARP for trapping on DNA and
causes cytotoxicity may have difference in the safety and efficacy with the PARPi. The PARPi have been
found its place in the all different types of breast cancers and have shown potential benefits. The purpose of
this review is to provide an update on the oral poly(ADP-ribose) polymerase (PARP) inhibitors for the improvement
in the treatment and management of breast cancer.
2025-02-01BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
Molecular mechanisms restoring olaparib efficacy through ATR/CHK1 pathway inhibition in olaparib-resistant BRCA1/2MUT ovarian cancer models
Article
作者: Mikula, Michał ; Statkiewicz, Małgorzata ; Gajek, Arkadiusz ; Szymczak-Pajor, Izabela ; Rusetska, Natalia ; Biegała, Łukasz ; Marczak, Agnieszka ; Rogalska, Aneta ; Śliwińska, Agnieszka
Resistance to olaparib inevitably develops in ovarian cancer (OC) patients, highlighting the necessity for effective strategies to improve its efficacy. Here, we established a novel olaparib-resistant patient-derived xenograft model of high-grade serous OC with BRCA1/2 mutations and examined the molecular characteristics of acquired resistance and resensitization to olaparib in treatment-naïve tumors in vivo. Olaparib-resistant xenografts were treated with olaparib, ATR inhibitor (ATRi, ceralasertib), CHK1 inhibitor (CHK1i, MK-8776) or their combinations. Proliferation, apoptosis, ATR/CHK1 activity, PARP signaling, DNA damage response (DDR), epithelial-to-mesenchymal transition (EMT), and MDR1 expression, were examined via RT-qPCR, western blot, and immunohistochemistry. Resistant tumors exhibited defects in PARP and ATR/CHK1 signaling, accompanied by altered expression of proteins involved in DDR and EMT. Olaparib rechallenge combined with ATR/CHK1 inhibitors showed promising synergistic effects on tumor growth inhibition. Mechanistically, combined treatments suppressed tumor proliferation without increasing apoptosis or necrosis, while inducing tumor cell vacuolization indicative of cell death. ATRi combined with olaparib induced or augmented downregulation of ATR, CHK1, PARP1, PARG, BRCA1, γH2AX, and PARylated protein expression, while reversing olaparib-induced upregulation of vimentin, BRCA2, and 53BP1. Our collective findings indicate that ATR/CHK1 pathway inhibition restores the olaparib efficacy in resistant BRCA1/2MUT high-grade serous OC, highlighting promising approach for olaparib rechallenge of non-responsive patients. Uncovered mechanisms might improve our understanding of acquisition and overcoming resistance to olaparib in ovarian cancer.
100 项与 奥拉帕利 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 |
|---|---|---|---|
| 晚期子宫内膜癌 | 欧盟 | 2024-08-15 | |
| 晚期子宫内膜癌 | 冰岛 | 2024-08-15 | |
| 晚期子宫内膜癌 | 列支敦士登 | 2024-08-15 | |
| 晚期子宫内膜癌 | 挪威 | 2024-08-15 | |
| 复发性子宫内膜癌 | 欧盟 | 2024-08-15 | |
| 复发性子宫内膜癌 | 冰岛 | 2024-08-15 | |
| 复发性子宫内膜癌 | 列支敦士登 | 2024-08-15 | |
| 复发性子宫内膜癌 | 挪威 | 2024-08-15 | |
| BRCA突变阳性乳腺癌 | 日本 | 2022-08-24 | |
| HRD 阳性卵巢癌 | 美国 | 2020-05-19 | |
| HRR 基因突变去势抵抗性前列腺癌 | 美国 | 2020-05-19 | |
| 胚系BRCA突变胰腺癌 | 美国 | 2019-12-27 | |
| 胰腺癌 | 韩国 | 2019-10-29 | |
| 前列腺癌 | 韩国 | 2019-10-29 | |
| 复发性HER2阴性乳腺癌 | 日本 | 2018-07-02 | |
| 复发性HER2阴性乳腺癌 | 日本 | 2018-07-02 | |
| 转移性胰腺腺癌 | 澳大利亚 | 2018-05-23 | |
| 乳腺癌 | 加拿大 | 2016-04-29 | |
| 卵巢癌 | 加拿大 | 2016-04-29 | |
| 转移性腺癌 | 欧盟 | 2014-12-16 |
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 |
|---|---|---|---|---|
| 去势抵抗性前列腺癌 | 申请上市 | 美国 | 2022-08-17 | |
| 子宫内膜癌 | 临床3期 | 法国 | 2024-06-26 | |
| 卵巢浆液性腺癌 | 临床3期 | 美国 | 2021-07-02 | |
| 卵巢浆液性腺癌 | 临床3期 | 中国 | 2021-07-02 | |
| 卵巢浆液性腺癌 | 临床3期 | 阿根廷 | 2021-07-02 | |
| 卵巢浆液性腺癌 | 临床3期 | 澳大利亚 | 2021-07-02 | |
| 卵巢浆液性腺癌 | 临床3期 | 奥地利 | 2021-07-02 | |
| 卵巢浆液性腺癌 | 临床3期 | 比利时 | 2021-07-02 | |
| 卵巢浆液性腺癌 | 临床3期 | 巴西 | 2021-07-02 | |
| 卵巢浆液性腺癌 | 临床3期 | 加拿大 | 2021-07-02 |
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临床结果
临床结果
适应症
分期
评价
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临床2期 | 14 | 糧壓構築鏇蓋齋蓋鑰構(蓋願糧觸鑰餘鑰鬱願窪) = 壓觸鑰鏇願蓋糧鑰衊網 壓齋壓憲積製積鹹淵鑰 (壓衊糧鬱繭淵願遞鏇鏇, 膚選廠襯積鏇鹹蓋齋廠 ~ 遞繭膚憲積廠製醖壓淵) 更多 | - | 2024-12-17 | |||
临床3期 | 卵巢癌 维持 | 806 | Olaparib plus Bevacizumab | 築鬱糧餘遞鑰憲顧餘衊(鬱簾願糧觸選鏇願構網) = mean Global Health Status and cognitive functioning seemed better with olaparib than bevacizumab alone 廠夢鏇繭蓋鬱鑰獵糧憲 (鏇窪憲廠簾願夢構製積 ) | 积极 | 2024-12-14 | |
Placebo | |||||||
临床3期 | - | 築鏇顧衊糧鏇襯選齋築(簾觸積淵衊鏇範衊範繭) = 淵獵壓築鏇壓遞製衊遞 夢壓鑰鬱願製鏇鹽築選 (鬱廠繭鏇顧窪膚鑰範廠 ) 更多 | 积极 | 2024-12-11 | |||
Placebo | 築鏇顧衊糧鏇襯選齋築(簾觸積淵衊鏇範衊範繭) = 鏇鹽蓋簾築顧網鹹廠憲 夢壓鑰鬱願製鏇鹽築選 (鬱廠繭鏇顧窪膚鑰範廠 ) 更多 | ||||||
临床3期 | - | 憲鏇餘襯憲壓遞壓膚鬱(憲蓋網繭醖範構齋願鹽) = met its primary endpoint of progression-free survival. 簾繭廠遞繭獵憲醖願積 (憲廠鹹鹽積鏇壓鑰構築 ) 达到 更多 | 积极 | 2024-12-09 | |||
KEYTRUDA+ Placebo | |||||||
临床2期 | homologous recombination deficiency | 114 | 餘蓋襯襯繭簾範鬱餘夢(艱齋鏇餘糧鑰願窪獵鹹) = 構範壓蓋窪淵夢選窪鏇 夢獵積淵憲憲觸蓋築簾 (憲簾衊製築襯遞夢獵憲, 11.8 ~ 88.2) | 积极 | 2024-12-01 | ||
临床3期 | 851 | Pembro+Olaparib (Pembro + Olaparib (Maintenance Phase)) | 餘繭選鬱獵鑰構遞選襯(膚願網願壓鹽選築夢鏇) = 艱網衊網夢壓蓋艱憲窪 醖餘憲構製繭築壓顧網 (襯廠鬱繭積齋願鹽淵廠, 醖壓製遞構構鏇醖憲遞 ~ 築築構壓選獵窪鬱網襯) 更多 | - | 2024-11-06 | ||
Placebo (Pembro + Placebo (Maintenance Phase)) | 餘繭選鬱獵鑰構遞選襯(膚願網願壓鹽選築夢鏇) = 築範範範遞積艱構膚積 醖餘憲構製繭築壓顧網 (襯廠鬱繭積齋願鹽淵廠, 遞獵積鹽襯憲製顧襯顧 ~ 窪遞構廠範鬱鑰糧膚簾) 更多 | ||||||
临床1期 | 130 | (refractory solid tumor + part A) | 繭鬱夢憲繭選簾廠蓋憲(鹹鹹衊廠艱鏇衊憲餘齋) = 構簾鏇獵膚餘選蓋鹹鏇 願鏇餘廠簾繭選糧獵鬱 (選鹹憲顧繭鹽鹽繭醖網 ) 更多 | 积极 | 2024-11-01 | ||
(platinum-sensitive extensive-stage or relapsed small-cell lung cancer + part B) | 繭鬱夢憲繭選簾廠蓋憲(鹹鹹衊廠艱鏇衊憲餘齋) = 網蓋選鑰衊艱願夢製鬱 願鏇餘廠簾繭選糧獵鬱 (選鹹憲顧繭鹽鹽繭醖網 ) 更多 | ||||||
临床3期 | 806 | Olaparib plus bevacizumab | 淵網獵膚窪願遞衊願壓(鏇製憲遞鏇餘齋獵積選) = 膚廠積糧獵製鏇淵願繭 夢餘窪醖衊蓋廠願簾夢 (淵糧構鏇餘齋顧衊築鬱 ) | 积极 | 2024-11-01 | ||
Platinum-based chemotherapy with PARP inhibitor rechallenge | 淵網獵膚窪願遞衊願壓(鏇製憲遞鏇餘齋獵積選) = 蓋願艱遞簾繭餘鏇鹹顧 夢餘窪醖衊蓋廠願簾夢 (淵糧構鏇餘齋顧衊築鬱 ) | ||||||
临床2期 | 非转移性前列腺癌 HRR alteration | BRCA2 alterations | 51 | 鹹積餘遞觸餘顧餘夢鬱(選艱壓築觸遞顧膚廠顧) = 蓋鬱夢餘膚遞襯範壓簾 艱膚鑰窪製構鹹選餘鑰 (蓋構鑰鬱遞選廠鑰選範 ) | 积极 | 2024-10-01 |
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