替扎他滨(Tezacitabine) - 药物靶点：POLA1 x 核糖核苷酸还原酶复合体_专利_临床

概要

基本信息

药物类型

小分子化药

别名

2'-Deoxy-2'-(fluoromethylene)cytidine、FMdc、Tezacitabine (USAN)

+ [5]

靶点

POLA1 x 核糖核苷酸还原酶复合体

作用机制

POLA1抑制剂(DNA聚合酶α亚基抑制剂)、RNR抑制剂(核糖核苷酸还原酶复合体抑制剂)

治疗领域

肿瘤消化系统疾病血液及淋巴系统疾病+ [1]

在研适应症-

非在研适应症

急性髓性白血病腺癌结肠癌+ [5]

原研机构

Sanofi

在研机构-

非在研机构

Sanofi

Chiron Corp.Kyowa Hakko Kogyo Co., Ltd.

+ [1]

最高研发阶段终止临床2期

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C10H14FN3O5

InChIKeyXPYQFIISZQCINN-QVXDJYSKSA-N

CAS号171176-43-5

关联

3

项与替扎他滨相关的临床试验

NCT00054873 / Completed临床2期

Tezacitabine With or Without 5-Fluorouracil (5-FU) for Advanced Esophageal Cancer or Gastric Cancer

The purpose of this study is to evaluate the efficacy and safety of tezacitabine when given alone or in combination with 5-fluorouracil (5-FU) to subjects who have advanced esophageal or gastric adenocarcinoma.

开始日期2003-11-01

申办/合作机构

Chiron Corp.

NCT00051688 / Terminated临床2期

Tezacitabine and Oxaliplatin for the Treatment of Patients With Metastatic Colorectal Cancer

The primary purpose of this study is to determine the best dose of tezacitabine when combined with oxaliplatin in patients with metastatic colorectal cancer. This study will also evaluate tumor response to the combination of anti-cancer drugs.

开始日期2003-06-01

申办/合作机构

Chiron Corp.

NCT00061620 / Completed临床1期IIT

Phase I Study of Continuous Infusion Schedule of (E)-2'-Deoxy-2'-(Fluoromethylene) Cytidine (Tezacitabine, FMdC) in Hematologic Malignancies

The goal of this clinical research study is to find the highest dose of Tezacitabine (FMdC) which can be safely given as a continuous infusion by vein to patients with hematologic malignancies. The general safety and effectiveness of this drug will also be studied.

开始日期2001-09-06

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+1]

100 项与替扎他滨相关的临床结果

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100 项与替扎他滨相关的转化医学

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100 项与替扎他滨相关的专利（医药）

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83

项与替扎他滨相关的文献（医药）

2023-11-01·Mutation Research/Genetic Toxicology and Environmental Mutagenesis

Hazard assessment of antineoplastic drugs and metabolites using cytotoxicity and genotoxicity assays

Article

作者: Reis, Rui M ; Serrano, Sergio V ; Klein, Mariana de Oliveira ; Gomes, Izabela Natália Faria ; Francisco, Luiza Flavia Veiga ; Silveira, Henrique C S

Antineoplastic drugs are among the most toxic pharmaceuticals. Their release into the aquatic ecosystems has been reported, giving rise to concerns about the adverse effects, including cytotoxicity and genotoxicity, that they may have on exposed organisms. In this study, we analyzed the cytotoxicity and genotoxicity of 5-fluorouracil (5-FU) and its metabolite alpha-fluoro-beta-alanine (3-NH2-F); gemcitabine (GEM) and its metabolite 2'-deoxy-2',2'-difluorouridine (2-DOH-DiF); as well as cyclophosphamide (CP) on the HepG2 cell line. Drug concentrations were based on those previously observed in the effluent of a major cancer hospital in Brazil. The study found that GEM, 2-DOH-DiF and 5-FU resulted in reduced cell viability. No reduction in cell viability was observed for CP and 3-NH2-F. Genotoxic assessment revealed damage in the form of nucleoplasmic bridges for CP and 3-NH2-F. The tested concentrations of all compounds resulted in significantly increased MNi and NBUDs. The results showed that these compounds induced cytotoxic and genotoxic effects in HepG2 cells at concentrations found in the environment. To the best of our knowledge, this study is the first to report on the cytogenotoxic impacts of the metabolites 3-NH2-F and 2-DOH-DiF in HepG2 cells. These findings may help in the development of public policies that could minimize potential environmental contamination.

2022-09-01·Chemosphere2区 · 环境科学与生态学

Functionalized metal-organic framework-derived carbon: Effective adsorbent to eliminate methylene blue, a small cationic dye from water

2区 · 环境科学与生态学

Article

作者: Jhung, Sung Hwa ; Hossain, Md Abul ; Mondol, Md Mahmudul Hassan

Elimination of organic dyes from wastewater is very important for our safe environment and sound health. In this work, adsorptive removal of cationic dyes, especially small ones, was investigated with carbonaceous materials to develop a competitive adsorption technology. To improve the performance of metal-organic framework (MOF)-derived carbons (MDCs) in dye adsorption, an MDC, derived from a MOF (MAF-6), was oxidatively functionalized with ammonium persulfate solutions (APSs). Although the porosity of pristine MDC decreased with functionalization via oxidation, functionalized MDCs (FMDCs), especially FMDC(1.0) that was obtained via treating MDC with APS (1.0 M), showed remarkable performances in the adsorption of small cationic dyes like methylene blue (MB) and azure B. For example, FMDC(1.0) had the maximum adsorption capacity (Q_o) of 625.0 mg/g (for MB) which is larger than any reported value with carbonaceous materials. Moreover, the obtained Q_o was around 4 and 2 times that of activated carbon with Q_o of 160 mg/g and MDC with Q_o of 298 mg/g, respectively. On the contrary, oxidative treatment of MDC was negative in adsorption of an anionic dye such as methyl orange. Moreover, the functionalized MDC was not very effective in the adsorption of cationic dyes with large sizes (like brilliant green, crystal violet, Janus green B, and rhodamine B) because of the limited pore size of the studied adsorbent FMDC(1.0). The remarkable adsorption of MB over FMDC(1.0) could be explained by electrostatic and π-π interactions. Finally, the facile recyclability of the FMDC(1.0) in MB adsorption was confirmed via successive adsorptions, FT-IR, and nitrogen adsorption; therefore, FMDC(1.0) can be suggested as a potential adsorbent to remove cationic dyes, especially with small molecular sizes.

2021-05-06·Chemistry – A European Journal

Structural Effects of Incorporation of 2'‐Deoxy‐2'2'‐Difluorodeoxycytidine (Gemcitabine) in A‐ and B‐Form Duplexes

Article

作者: Martín‐Pintado, Nerea ; Aviñó, Anna ; González, Carlos ; Mazzini, Stefania ; Cabrero, Cristina ; Gargallo, Raimundo ; Eritja, Ramon

AbstractWe report the structural effect of 2'‐deoxy‐2',2'‐difluorocytidine (dFdC) insertions in the DNA strand of a DNA : RNA hybrid duplex and in a self‐complementary DNA : DNA duplex. In both cases, the modification slightly destabilizes the duplex and provokes minor local distortions that are more pronounced in the case of the DNA : RNA hybrid. Analysis of the solution structures determined by NMR methods show that dFdC is an adaptable derivative that adopts North type sugar conformation when inserted in pure DNA, or a South sugar conformation in the context of DNA : RNA hybrids. In this latter context, South sugar pucker favors the formation of a 2'F⋅⋅H8 attractive interaction with a neighboring purine, which compensates the destabilizing effect of base pair distortions. These interactions share some features with pseudohydrogen bonds described previously in other nucleic acids structures with fluorine modified sugars.

100 项与替扎他滨相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D06100	替扎他滨	-	DB06433

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
胃癌	临床2期	美国	Chiron Corp.	2003-11-01
转移性结直肠癌	临床2期	美国	Chiron Corp.	2003-06-01
急性髓性白血病	临床2期	美国	-	-
结肠癌	临床2期	-	Matrix Pharmaceutical, Inc.	-
结肠癌	临床2期	-	Sanofi	-
结肠癌	临床2期	-	Kyowa Hakko Kogyo Co., Ltd.	-
非小细胞肺癌	临床2期	美国	-	-
非小细胞肺癌	临床2期	-	Sanofi	-
非小细胞肺癌	临床2期	-	Kyowa Hakko Kogyo Co., Ltd.	-
非小细胞肺癌	临床2期	-	Matrix Pharmaceutical, Inc.	-