更新于：2024-12-12
Palifosfamide Tromethamine
更新于：2024-12-12
概要
基本信息
原研机构 |
最高研发阶段临床前 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评孤儿药 (美国) |
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结构
分子式C8H22Cl2N3O5P |
InChIKeyPGLRCMRTUIMSFQ-UHFFFAOYSA-N |
CAS号1070409-31-2 |
关联
13
项与 Palifosfamide Tromethamine 相关的临床试验A Phase II Randomized, Open Label Study of Ad-RTS-hIL-12 Monotherapy or Combination With Palifosfamide in Subjects With Recurrent/Metastatic Breast Cancer and Accessible Lesions
Multicenter Single Arm Phase II Study of Single Agent Palifosfamide in Recurrent and Incurable Germ Cell Tumors
A Multi-center, Open-Label, Adaptive, Randomized Study of Palifosfamide-tris, a Novel DNA Crosslinker, in Combination With Carboplatin and Etoposide (PaCE) Chemotherapy Versus Carboplatin and Etoposide (CE) Alone in Chemotherapy Naïve Patients With Extensive-Stage Small Cell Lung Cancer. The MATISSE Study
100 项与 Palifosfamide Tromethamine 相关的临床结果
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100 项与 Palifosfamide Tromethamine 相关的转化医学
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100 项与 Palifosfamide Tromethamine 相关的专利（医药）
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54
项与 Palifosfamide Tromethamine 相关的文献（医药）2023-04-01Environmental science and pollution research international
Environmental performance of phytosanitary control techniques on soybean crop estimated by life cycle assessment (LCA).
Article
作者: Ventura, Mauricio Ursi ; Mrtvi, Paulo Roberto ; Barizon, Robson Rolland Monticelli ; Possamai, Edivan Jose ; Ralisch, Ricardo ; Folegatti-Matsuura, Marilia Ieda da Silveira ; Lucas, Kassio Ricardo Garcia
Phytosanitary control is essential to ensure agricultural productivity and quality. However, approaches based on scheduled use of pesticides, overuse of harmful molecules produce impacts on different types of living organisms. Integrated Pest and Disease Management (IPM-IDM) may significantly reduce the burden of pesticides in the environment. Plant resistance may also be included in the IPM-IDM and even in conventional management due to little requirement of additional knowledge and changes in agricultural practices. Robust environmental assessments using methodology of universal use, life cycle assessment (LCA), may estimate the impacts of specific pesticides that cause major damages, including remarkable category impacts. Therefore the objective of this study was to determine the impacts and (eco)toxicological effects of phytosanitary strategies (IPM-IDM including or not lepidopteran resistant transgenic cultivars) vs. the scheduled approach. Two inventory modeling methods were also applied to gather information on the use and applicability of these methods. Life cycle assessment (LCA) was applied using two inventory modeling methods: 100%Soil and PestLCI (Consensus) using data from Brazilian croplands under tropical conditions, by combining phytosanitary approaches (IPM-IDM, IPM-IDM + transgenic cultivar, conventional, conventional + transgenic cultivar) and modeling methods. Hence, eight soybean production scenarios were established. The IPM-IDM was efficient to reduce the (eco)toxicity impacts of soybean production mainly for freshwater ecotoxicity category. Due to the dynamic character of IPM-IDM approaches, the inclusion of recently introduced strategies (plant resistant and biological control to stink bugs and plant fungal diseases) may diminish even more the principal impacting substances throughout the Brazilian croplands. The PestLCI Consensus method, although its development is yet in progress, to date can be suggested to estimate the agriculture environmental impacts more properly under tropical conditions.
2021-12-01Journal of the Egyptian National Cancer Institute
An in vitro cytotoxicity of glufosfamide in HepG2 cells relative to its nonconjugated counterpart
Article
作者: Rashidi, Fatma B ; Mohamed, Amr S ; Abdelhakim, Heba K ; Ahmed, Doaa E ; Arafa, Hossam M M
Abstract:
Background:
Glufosfamide (β-d-glucosylisophosphoramide mustard, GLU) is an alkylating cytotoxic agent in which ifosforamide mustard (IPM) is glycosidically linked to the β-d-glucose molecule. GLU exerted its cytotoxic effect as a targeted chemotherapy. Although, its cytotoxic efficacy in a number of cell lines, there were no experimental or clinical data available on the oncolytic effect of oxazaphosphorine drugs in hepatocellular carcinoma. Therefore, the main objective of the current study is to assess the cytotoxic potential of GLU for the first time in the hepatocellular carcinoma HepG2 cell line model.
Methods:
Cytotoxicity was assayed by the MTT method, and half-maximal inhibitory concentration (IC50) was calculated. Flow cytometric analysis of apoptosis frequencies was measured by using Annexin V/PI double stain, an immunocytochemical assay of caspase-9, visualization of caspase-3, and Bcl2 gene expression were undertaken as apoptotic markers. Mitochondrial membrane potential was measured using the potentiometric dye; JC-1, as a clue for early apoptosis as well as ATP production, was measured by the luciferase-chemiluminescence assay.
Results:
Glufosfamide induced cytotoxicity in HepG2 cells in a concentration- and time-dependent manner. The IC50 values for glufosfamide were significantly lower compared to ifosfamide. The frequency of apoptosis was much higher for glufosfamide than that of ifosfamide. The contents of caspase-9 and caspase-3 were elevated following exposure to GLU more than IFO. The anti-apoptotic Bcl2 gene expression, the mitochondrial membrane potential, and the cellular ATP levels were significantly decreased than in case of ifosfamide.
Conclusions:
The current study reported for the first time cytotoxicity activity of glufosfamide in HepG2 cells in vitro. The obtained results confirmed the higher oncolytic activity of glufosfamide than its aglycone ifosfamide. The generated data warrants further elucidations by in vivo study.
2021-12-01Molecular cancer therapeutics2区 · 医学
Predictive Value of MRP-1 in Localized High-Risk Soft Tissue Sarcomas: A Translational Research Associated to ISG-STS 1001 Randomized Phase III Trial
2区 · 医学
Article
作者: Gutierrez, Antonio ; Hindi, Nadia ; Braglia, Luca ; Lopez-Alvarez, Maria ; Dei Tos, Angelo Paolo ; Palmerini, Emanuela ; Lopez-Lopez, Daniel ; Lopez-Pousa, Antonio ; Dopazo, Joaquin ; Moura, David S. ; Barisella, Marta ; Gronchi, Alessandro ; Casali, Paolo G. ; Bagué, Silvia ; Quagliuolo, Vittorio L. ; Collini, Paola ; Blay, Jean-Yves ; Stacchiotti, Silvia ; Romagosa, Cleofe ; Renne, Salvatore L. ; Coindre, Jean-Michel ; Gambarotti, Marco ; Martin-Broto, Javier ; Valverde, Claudia ; Picci, Piero ; Grignani, Giovanni ; Merlo, Domenico Franco ; Brunello, Antonella ; Ramos, Rafael ; Velasco, Valerie
Abstract:
MRP-1 is implicated in multidrug resistance and was described as prognostic in high-risk patients with soft-tissue sarcoma (STS) in a previous study. The current research aimed to validate MRP-1 prognostic/predictive value in localized sarcomas treated with anthracyclines plus ifosfamide within the ISG-1001 phase III study. In addition, the inhibitory activity on MRP-1 was investigated in preclinical studies to identify new combinations able to increase the efficacy of standard chemotherapy in STS. MRP-1 expression was assessed by IHC in tissue microarrays from patients with STS and tested for correlation with disease-free survival (DFS) and overall survival (OS). In vitro studies tested the efficacy of MRP-1 inhibitors (nilotinib, ripretinib, selumetinib, and avapritinib) in sarcoma cell lines. The effect of combinations of the most active MRP-1 inhibitors and chemotherapy was measured on the basis of apoptosis. MRP-1 was evaluable in 231 of 264 cases who entered the study. MRP-1 expression (strong intensity) was independently associated with worse DFS [HR, 1.78; 95% confidence interval (CI), 1.11–2.83; P = 0.016], in the multivariate analysis, with a trend for a worse OS (HR, 1.78; 95% CI, 0.97–3.25; P = 0.062). In vitro studies showed that the addition of MRP-1 inhibitors (nilotinib or avapritinib) to doxorubicin plus palifosfamide, significantly increased cell death in SK-UT-1 and CP0024 cell lines. MRP-1 is an adverse predictive factor in localized high-risk patients with STS treated with neoadjuvant anthracyclines plus ifosfamide followed by surgery. In vitro findings support the clinical assessment of the combination of chemotherapy and MRP-1 inhibitors as a promising strategy to overcome the drug ceiling effect for chemotherapy.
1
项与 Palifosfamide Tromethamine 相关的新闻（医药）100 项与 Palifosfamide Tromethamine 相关的药物交易
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研发状态
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 |
|---|---|---|---|---|
| 广泛期小细胞肺癌 | 临床3期 | 美国 | 2012-05-01 | |
| 广泛期小细胞肺癌 | 临床3期 | 澳大利亚 | 2012-05-01 | |
| 广泛期小细胞肺癌 | 临床3期 | 加拿大 | 2012-05-01 | |
| 广泛期小细胞肺癌 | 临床3期 | 法国 | 2012-05-01 | |
| 广泛期小细胞肺癌 | 临床3期 | 匈牙利 | 2012-05-01 | |
| 广泛期小细胞肺癌 | 临床3期 | 以色列 | 2012-05-01 | |
| 广泛期小细胞肺癌 | 临床3期 | 意大利 | 2012-05-01 | |
| 广泛期小细胞肺癌 | 临床3期 | 波兰 | 2012-05-01 | |
| 广泛期小细胞肺癌 | 临床3期 | 俄罗斯 | 2012-05-01 | |
| 广泛期小细胞肺癌 | 临床3期 | 中国台湾 | 2012-05-01 |
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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3期 | 188 | 艱遞夢淵鬱鏇範鹹襯願(鏇膚顧襯齋窪選齋壓壓) = 鹽選鏇蓋觸鹽壓壓廠鹹 窪衊選製夢觸鹹觸願憲 (廠衊繭遞蓋夢製繭蓋獵 ) | 不佳 | 2017-08-10 | |||
艱遞夢淵鬱鏇範鹹襯願(鏇膚顧襯齋窪選齋壓壓) = 窪積齋衊膚壓憲鑰鬱衊 窪衊選製夢觸鹹觸願憲 (廠衊繭遞蓋夢製繭蓋獵 ) | |||||||
临床3期 | 447 | 獵醖膚築壓範鹹壓觸壓(憲醖遞憲簾衊蓋選淵願) = 餘鬱糧夢壓觸糧鬱鏇鑰 醖構艱製鹽構蓋簾鹹鬱 (構遞蓋襯願選餘鏇糧壓 ) 更多 | 不佳 | 2016-11-10 | |||
Doxorubicin+Placebo | 獵醖膚築壓範鹹壓觸壓(憲醖遞憲簾衊蓋選淵願) = 餘醖齋鏇廠遞選鏇憲鏇 醖構艱製鹽構蓋簾鹹鬱 (構遞蓋襯願選餘鏇糧壓 ) 更多 | ||||||
临床2期 | 5 | 遞網餘衊遞獵鑰鹹醖淵(醖蓋膚蓋選觸醖鑰範夢) = 餘觸鬱簾獵衊淵鬱餘廠 鑰窪範夢構網積繭製積 (餘鏇觸廠簾構觸遞鑰顧, 構鏇窪淵繭鬱鏇簾齋獵 ~ 鏇願餘簾鬱衊獵夢製願) 更多 | - | 2015-07-02 | |||
临床3期 | 广泛期小细胞肺癌 一线 | 188 | 廠齋鬱窪衊憲糧鑰繭鏇(構鑰夢構糧艱鬱築鏇淵) = 淵鑰鏇憲衊繭獵顧築顧 憲鏇遞鹹鏇糧願衊鹹餘 (顧構鬱構廠積餘鏇選選 ) | 不佳 | 2015-05-20 | ||
廠齋鬱窪衊憲糧鑰繭鏇(構鑰夢構糧艱鬱築鏇淵) = 製餘構廠廠築網築膚艱 憲鏇遞鹹鏇糧願衊鹹餘 (顧構鬱構廠積餘鏇選選 ) | |||||||
临床2期 | 肉瘤 二线 | - | 顧窪醖艱繭餘壓願憲鏇(淵顧築鹹餘顧鹽築餘鹽) = 蓋糧顧糧齋壓鏇選觸窪 鑰選膚夢衊壓遞獵醖鹹 (構淵積顧願襯獵鬱廠鹹 ) | 积极 | 2010-05-20 | ||
顧窪醖艱繭餘壓願憲鏇(淵顧築鹹餘顧鹽築餘鹽) = 憲壓夢蓋積簾齋選夢選 鑰選膚夢衊壓遞獵醖鹹 (構淵積顧願襯獵鬱廠鹹 ) | |||||||
临床1期 | 13 | 觸艱蓋夢網觸鬱壓遞醖(壓餘齋壓糧鏇醖築遞選) = 夢積壓糧齋觸構鬱築艱 壓積齋鹽獵齋鹽繭廠糧 (積簾積齋範夢膚淵獵繭 ) | - | 2009-05-20 | |||
临床1期 | 18 | 廠艱鏇顧衊鑰網願襯積(廠糧醖鑰築鹽餘糧糧艱) = 積憲糧鏇鬱窪醖簾膚襯 廠齋鹹醖網鹹積築鹹憲 (夢窪蓋窪艱鹽鑰窪遞構 ) 更多 | - | 2006-06-20 | |||
临床1期 | - | Isophosphoramide mustard-lysine (IPM-L; ZIO-201) | 顧鹹鏇醖衊鬱遞醖簾鹽(鏇積鏇繭齋願積淵網淵) = 鹽築鏇襯壓鏇網醖製艱 獵構醖醖糧繭襯糧築膚 (廠遞選衊鑰齋窪網窪壓 ) 更多 | - | 2006-02-01 | ||
Cyclophosphamide (CPA) | 選餘醖構醖鬱衊觸積鬱(壓壓糧膚築繭鏇壓遞獵) = 夢淵繭襯構憲壓鹹鏇鬱 積網願蓋遞淵鹽鏇淵憲 (繭積築鬱窪簾壓艱製齋 ) 更多 |
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