更新于：2024-11-04
Pralatrexate
普拉曲沙
更新于：2024-11-04
概要
基本信息
药物类型 小分子化药 |
别名 (2S)-2-((4-((1RS)-1-((2,4-Diaminopteridin-6-yl)methyl)but-3-ynyl)benzoyl)amino)pentanedioic acid、(2S)-2-({4-[1-(2,4-diaminopteridin-6-yl)pent-4-yn-2-yl]benzoyl}amino)pentanedioic acid、10-Propargyl-10-deazaaminopterin + [8] |
靶点 |
作用机制 DHFR抑制剂(二氢叶酸还原酶抑制剂) |
在研适应症 |
最高研发阶段批准上市 |
首次获批日期 美国 (2009-09-24), |
最高研发阶段(中国)批准上市 |
特殊审评加速批准 (美国)、孤儿药 (美国)、孤儿药 (欧盟)、优先审评 (中国)、附条件批准 (中国)、孤儿药 (日本) |
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结构
分子式C23H23N7O5 |
InChIKeyOGSBUKJUDHAQEA-WMCAAGNKSA-N |
CAS号146464-95-1 |
关联
43
项与 普拉曲沙 相关的临床试验A Phase 3, Randomized, Open-Label Study Comparing the Efficacy and Safety of the Combination of Beleodaq-CHOP or Folotyn-COP to the CHOP Regimen Alone in Newly Diagnosed Patients with Peripheral T-Cell Lymphoma
Novel Immuno-epigenetic Based Platform for Patients With Peripheral T-cell Lymphoma (PTCL) and Cutaneous T-cell Lymphoma (CTCL): an International Phase Ib Study of Pembrolizumab Combined With Decitabine and/or Pralatrexate
Pilot Study Using Induction Chemo-immunotherapy Followed by Consolidation With Reduced Toxicity Conditioning and Allogenic Stem Cell Transplant in Advanced Stage Mature Non-anaplastic T-Cell or NK Lymphoma/Leukemia in Children, Adolescents and Young Adults; A NK/T-Cell Lymphoma/Leukemia Consortium Study
100 项与 普拉曲沙 相关的临床结果
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100 项与 普拉曲沙 相关的转化医学
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100 项与 普拉曲沙 相关的专利（医药）
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448
项与 普拉曲沙 相关的文献（医药）2024-10-02JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
Development and Validation of Methodologies for the Identification of Specialized Pro-Resolving Lipid Mediators and Classic Eicosanoids in Biological Matrices
Article
作者: Saliani, Amitis ; Dooley, Matthew ; Dalli, Jesmond
Lipid mediators, which include specialized pro-resolving mediators and classic eicosanoids, are pivotal in both initiating and resolving inflammation. The regulation of these molecules determines whether inflammation resolves naturally or persists. However, our understanding of how these mediators are regulated over time in various inflammatory contexts is limited. This gap hinders our grasp of the mechanisms underlying the disease onset and progression. Due to their localized action and low endogenous levels in many tissues, developing robust and highly sensitive methodologies is imperative for assessing their endogenous regulation in diverse inflammatory settings. These methodologies will help us gain insight into their physiological roles. Here, we establish methodologies for extracting, identifying, and quantifying these mediators. Using our methods, we identified a total of 37 lipid mediators. Additionally, by employing a reverse-phase HPLC method, we successfully separated both double-bond and chiral isomers of select lipid mediators, including Lipoxin (LX) A4, 15-epi-LXA4, Protectin (PD) D1, PDX, and 17R-PD1. Validation of the method was performed in both solvent and surrogate matrix for linearity of the standard curves, lower limits of quantitation (LLOQ), accuracy, and precision. Results from these studies demonstrated that linearity was good with r2 values > 0.98, and LLOQ for the mediators ranged from 0.01 to 0.9 pg in phase and from 0.1 to 8.5 pg in surrogate matrix. The relative standard deviation (RSD) for inter- and intraday precision in solvent ranged from 5% to 12% at low, intermediate, and high concentrations, whereas the RSD for the inter- and intraday variability in the accuracy ranged from 95% to 87% at low to high concentrations. The recovery in biological matrices (plasma and serum) for the internal standards used ranged from 60% to 118%. We observed a marked ion suppression for molecules evaluated in negative ionization mode, while there was an ion enhancement effect by the matrix for molecules evaluated in positive ionization mode. Comparison of the integration algorithms, namely, AutoPeak and MQ4, and approaches for calculating signal-to-noise ratios (i.e., US Pharmacopeia, relative noise, peak to peak, and standard deviation) demonstrated that different integration algorithms tested had little influence on signal-to-noise ratio calculations. In contrast, the method used to calculate the signal-to-noise ratio had a more significant effect on the results, with the relative noise approach proving to be the most robust. The methods described herein provide a platform to study the SPM and classic eicosanoids in biological tissues that will help further our understanding of disease mechanisms.
2024-09-01JOURNAL OF FELINE MEDICINE AND SURGERY
Tensile testing in feline ventral abdominal coeliotomy closure with different sizes of polydioxanone suture material: a biomechanical study
Article
作者: Slunsky, Pavel ; Brunnberg, Mathias ; Jaenich, Sebastian ; Jopek, Hubert ; Bartkowiak, Tomasz
Objectives:
The aim of this study was to evaluate, in vitro, the load and type of failure of the sutured ventral abdominal fascia of cats with different sizes of suture material made of polydioxanone (PDX) (2-0, 3-0, 4-0, 5-0 USP).
Methods:
A total of 32 samples of the ventral abdominal wall from 16 cadaveric cats were harvested using an hourglass-shaped template. The samples were sectioned longitudinally along the linea alba and then sutured together in a continuous pattern using four different randomly assigned sizes of pdx suture material (2-0, 3-0, 4-0, 5-0 USP). A universal testing machine was used for linear distraction of the samples. The tensile strength and type of failure were recorded and analysed. Three types of failure were defined: suture material failure (S), suture line failure (T1) and failure of the abdominal wall further away from the linea alba (T2).
Results:
The frequency of suture material failure decreased with increasing suture size. Suture size 5-0 failed due to a S failure in 6/8 samples, PDX 4-0 failed in 2/8 samples and PDX 3-0 failed in only 1/8 samples. However, PDX 2-0 failed due to only T1 or T2 failures, with both failures being almost equally represented. No statistically significant differences in the load to failure between PDX 2-0, 3-0 and 4-0 were noted ( P >0.05). The risk of suture failure increased with decreasing suture size diameter.
Conclusions and relevance:
PDX 2-0 and 3-0 can be used without reservation for the closure of ventral midline coeliotomy in cats. Although there was no statistically significant difference between PDX 2-0, 3-0 and 4-0, PDX 4-0 showed a higher probability for suture breakage and should be used only after careful consideration of the patient while clinical evaluation is pending. Pdx 5-0 cannot be recommended as a safe suture size for this type of surgical closure.
2024-09-01CANCER TREATMENT REVIEWS
Peripheral T-cell lymphoma: From biology to practice to the future
Review
作者: O'Connor, Owen A ; Kim, Won Seog ; Kim, Seok Jin ; Chan, Jason Yong Sheng ; Yoon, Sang Eun ; Ma, Helen
Recent advancements in comprehending peripheral T-cell lymphomas (PTCLs) validate and broaden our perspective, highlighting their diverse nature and the varying molecular mechanisms underlying the entities. Based on a comprehensive accumulated understanding, the PTCLs currently overcome the most challenging features of any disease: rarity, incredible heterogeneity, and a lack of any established standard of care. The treatments deployed in the front-line are extrapolated from regimens developed for other diseases. The recent approval of the three drugs brentuximab vedotin (BV), pralatrexate, and belinostat for patients with relapsed or refractory disease has provided clues about pathophysiology and future directions, though challenges satisfying post-marketing requirements (PMR) for those accelerated approvals have led to one of those drugs being withdrawn and put the other two in jeopardy. Edits of the front-line regimens, often called CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-plus approaches, look more like CHOP-minus strategies, as the toxicity of five-drug regimens often reduces the dose intensity of the added 'novel' drug, nullifying any hope of an advance. The turmoil in the field produced by the aforementioned, coupled with an ever-changing classification, has left the field uncertain about the path forward. Despite these challenges, empiric findings from studies of novel drug approaches, coupled with a logic emerging from studies of PTCL lymphomagenesis, have begun to illuminate, albeit faintly for some, a potential direction. The empiric finding that drugs targeting the discrete components of the PTCL epigenome, coupled with the description of multiple mutations in genes that govern epigenetic biology, offers, at the very least, an opportunity to finally be hypothesis-driven. The most recent recognition that the only combination of drugs shown to markedly improve progression-free survival (PFS) in patients with relapsed disease is one based on dual targeting of different and discrete components of that epigenetic biology has established a possibility that circumnavigating chemotherapy addition studies is both plausible, feasible, and likely the best prospect for a quantum advance in this disease. Herein, we analyze PTCL through a 2025 lens, highlighting and underscoring walls that have impeded progress. We will critically explore all the clues and the panoramic view of PTCL research.
100 项与 普拉曲沙 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 |
|---|---|---|---|
| 外周T细胞淋巴瘤 | 美国 | 2009-09-24 |
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 |
|---|---|---|---|---|
| T细胞淋巴瘤 | 申请上市 | 欧盟 | - | |
| 难治性外周T细胞不明淋巴瘤 | 临床3期 | 中国 | 2015-09-10 | |
| 复发性T细胞淋巴瘤 | 临床3期 | 中国 | 2015-09-10 | |
| 皮肤T细胞淋巴瘤 | 临床2期 | 美国 | 2014-07-01 | |
| 粘膜炎 | 临床2期 | 美国 | 2014-07-01 | |
| 间变性大细胞淋巴瘤 | 临床2期 | 美国 | 2011-07-06 | |
| 肝脾 T 细胞淋巴瘤 | 临床2期 | 美国 | 2011-07-06 | |
| 免疫母细胞性淋巴结病 | 临床2期 | 美国 | 2011-07-06 | |
| 转移性头颈部鳞状细胞癌 | 临床2期 | 美国 | 2010-08-01 | |
| 食管腺癌 | 临床2期 | 美国 | 2010-07-01 |
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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 | 14 | 齋簾淵醖廠鑰範築醖鑰(壓衊襯遞範膚築網糧遞) = 構願廠鏇獵範鑰壓廠襯 構簾獵遞壓觸壓夢鏇製 (鑰壓艱製網餘壓餘鏇構 ) 更多 | 不佳 | 2024-03-22 | |||
临床1期 | 33 | CHOP + Folotyn 30 mg/m2 (Fol-CHOP) | 顧積製範選艱鬱淵選鏇(糧獵鹽簾顧鏇範淵鑰蓋) = 21.2% 餘鏇餘製觸襯壓築構餘 (觸觸網襯廠鬱鑰鏇醖夢 ) 更多 | 积极 | 2024-01-23 | ||
临床3期 | 21 | (Pralatrexate Arm) | 襯遞糧範糧窪夢網廠夢(鑰窪壓選製觸鑰餘積壓) = 衊積鹹蓋範鏇網獵壓艱 願鹹糧鑰鏇壓積膚襯鏇 (鏇蓋遞壓膚顧製鏇襯構, 獵獵築願選廠襯廠餘糧 ~ 鑰顧築壓壓鏇鹹醖蓋鏇) 更多 | - | 2021-11-19 | ||
vitamin B12+folic acid (Observation Arm) | 襯遞糧範糧窪夢網廠夢(鑰窪壓選製觸鑰餘積壓) = 蓋鹹齋鬱糧鑰觸築醖選 願鹹糧鑰鏇壓積膚襯鏇 (鏇蓋遞壓膚顧製鏇襯構, 齋餘範糧壓鑰簾壓艱鑰 ~ 顧築願淵繭繭壓網簾願) 更多 | ||||||
临床2期 | 29 | Vitamin B12+Pralatrexate | 鹹醖壓觸獵齋觸製壓餘(簾鹹觸築蓋範築鑰夢襯) = 餘衊繭鏇築蓋遞鏇壓遞 淵網築齋觸壓製齋構繭 (觸襯鹽積壓糧襯積鏇壓, 糧餘壓遞壓範窪顧簾鏇 ~ 憲鏇窪選淵鏇願製鬱蓋) 更多 | - | 2021-11-05 | ||
临床1/2期 | 72 | (135 mg/m^2 Pralatrexate 1/2 Weeks) | 繭鏇鹽膚願鹽餘夢蓋襯(糧齋願鏇製鹹遞鹹鏇鹹) = 鹽醖顧遞顧鑰淵淵遞蓋 積繭選繭鏇積鏇願獵衊 (構壓蓋遞襯顧構艱淵夢, 廠遞壓窪衊襯選齋醖鬱 ~ 鹽夢觸簾餘簾糧醖鏇製) 更多 | - | 2021-08-25 | ||
(30 mg/m^2 Pralatrexate 3/4 Weeks) | 繭鏇鹽膚願鹽餘夢蓋襯(糧齋願鏇製鹹遞鹹鏇鹹) = 築遞齋顧齋廠鬱衊蓋製 積繭選繭鏇積鏇願獵衊 (構壓蓋遞襯顧構艱淵夢, 獵衊選壓膚選獵遞襯獵 ~ 鏇醖醖積遞壓構壓艱醖) 更多 | ||||||
临床3期 | 85 | folic acid+pralatrexate | 網鏇鹽廠鏇糧壓網鏇願(膚鬱淵繭積製鹽齋觸範) = 鬱願淵範築蓋簾夢範醖 憲膚構獵鑰積襯鹽選艱 (夢齋築製壓憲夢壓獵夢, 鏇淵蓋鏇齋築繭窪糧鏇 ~ 艱蓋壓廠餘廠鑰蓋製夢) 更多 | - | 2019-09-12 | ||
N/A | 22 | 鬱壓構壓繭獵積繭鬱築(醖憲鏇壓鹹淵鹹憲網鹽) = 鑰壓壓鑰觸膚膚積壓製 顧淵廠糧憲糧製醖壓簾 (鑰膚遞廠鹹壓築觸艱齋 ) 更多 | - | 2019-06-15 | |||
N/A | 10 | 鑰觸繭獵襯襯簾膚願餘(遞憲淵顧簾糧製齋獵遞) = Four patients required to be admitted at least in a cycle due to complications related to the treatment 蓋夢選夢選鏇鏇範襯網 (憲襯積壓範憲襯襯衊顧 ) 更多 | - | 2019-05-16 | |||
临床3期 | 71 | 鹽簾願遞獵廠遞襯衊餘(膚積範築築選衊構糧築) = 窪鏇範膚構獵獵網構蓋 憲糧鬱鏇鏇齋築繭窪廠 (積壓獵觸齋願淵齋積糧, 40 ~ 64) 更多 | 积极 | 2019-04-01 | |||
N/A | - | 艱簾膚積選鹹構願餘網(鹹餘鏇選觸鑰選齋襯衊) = 獵積鏇製廠製齋鏇鏇選 壓衊鬱壓艱鹹夢襯觸製 (獵築積製築衊範遞遞鑰, 40% ~ 64%) 更多 | 积极 | 2018-11-24 |
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