FdCyd(FdCyd) - 药物靶点：DNMT1_专利_临床

概要

基本信息

药物类型

小分子化药

别名

5-fluoro-2'-deoxycytidine、5-fluoro-2-deoxycytidine、5-fluorodeoxycytidine

+ [3]

靶点

DNMT1

作用机制

DNMT1抑制剂(DNA（胞嘧啶-5）-甲基转移酶-1抑制剂)

治疗领域

肿瘤呼吸系统疾病皮肤和肌肉骨骼疾病+ [2]

在研适应症-

非在研适应症

成人急性髓性白血病晚期癌症晚期非小细胞肺癌+ [6]

原研机构

City of Hope National Medical Center

在研机构-

非在研机构

City of Hope National Medical Center

National Cancer Institute

最高研发阶段无进展临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C9H12FN3O4

InChIKeyIDYKCXHJJGMAEV-RRKCRQDMSA-N

CAS号10356-76-0

关联

5

项与 FdCyd 相关的临床试验

NCT01534598

/ Completed临床1期IIT

Phase I Trial of Oral 5-Fluoro-2'-Deoxycytidine With Oral Tetrahydrouridine in Patients With Advanced Solid Tumors

Background:
- FdCyd (also called 5-fluoro-2'-deoxycytidine) and THU (also called tetrahydrouridine) are experimental cancer treatment drugs. FdCyd may change how genes work in cancer cells. THU helps keep FdCyd from being broken down by the body. FdCyd and THU have been given to people on other cancer treatment trials, usually by vein. Researchers want to give FdCyd and THU by mouth to see if they work against cancers that have not responded to earlier treatments.
Objectives:
- To test oral FdCyd and THU on advanced solid tumors that have not responded to earlier treatments.
Eligibility:
- Individuals at least 18 years of age who have advanced solid tumors that have not responded to standard treatments.
Design:
* Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies and tumor samples will used to study the cancer before treatment.
* FdCyd and THU will be given in 21-day cycles. THU should be taken 30 minutes before taking FdCyd.
* Participants will take FdCyd and THU by mouth, once a day, for 3 days at the beginning of the first and second weeks of each cycle (days 1 3 and 8 10). The drugs will not be taken during the entire third week of each cycle.
* Treatment will be monitored with frequent blood tests and imaging studies.
* Treatment will continue as long as the cancer is responding to the drugs and serious side effects do not develop....

开始日期2012-03-05

申办/合作机构

National Cancer Institute

NCT01479348

/ Terminated早期临床1期IIT

Phase 0 Trial of [F-18]-5-Fluoro-2'-Deoxycytidine With Tetrahydrouridine

Background:
- The drugs FdCyd (also called 5-fluoro-2'-deoxycytidine) and THU (also called tetrahydrouridine) are being used in a cancer treatment study. Not a lot is known about how FdCyd works in the body. Researchers want to look at a modified form of FdCyd using imaging studies to see how the drug reacts with the cancer. This study is not a treatment study. It is open only to people who are already on the FdCyd and THU cancer treatment study.
Objectives:
- To study how FdCyd affects advanced cancer cells.
Eligibility:
- Participants in National Cancer Institute study 09-C-0214.
Design:
Participants will have two imaging studies, one before starting FdCyd and THU treatment and one after starting treatment.
Participants will have the modified FdCyd, known as F-18 FdCyd, with a dose of THU. The doses will be followed by two imaging study scans and frequent blood samples.
This procedure will be repeated at a later date, during the FdCyd and THU treatment period.
Treatment will not be provided as part of this study. This is an imaging study protocol only....

开始日期2011-11-01

申办/合作机构

National Cancer Institute

NCT01041443

/ Completed临床1期IIT

A Phase I Study of 5-Fluoro-2'-Deoxycytidine With Tetrahydrouridine (FdCyd + THU) in Myeloid Leukemia and MDS

This phase I trial is studying the side effects and best dose of 5-Fluoro-2'-deoxycytidine (FdCyd) when given together with tetrahydrouridine (THU) in treating patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). FdCyd may inhibit cancer cell growth by increasing the production in cells of compounds that suppress growth or by otherwise killing cells. Although FdCyd is stable as a drug solution, it is rapidly inactivated by an enzyme present in people. THU is included in the treatment to inhibit the enzyme, prolonging the time FdCyd remains in the body

开始日期2009-12-01

申办/合作机构

City of Hope National Medical Center

100 项与 FdCyd 相关的临床结果

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100 项与 FdCyd 相关的转化医学

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100 项与 FdCyd 相关的专利（医药）

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135

项与 FdCyd 相关的文献（医药）

2024-08-09·ACS Pharmacology & Translational Science

Epigenetic Targeting of Heparan Sulfate 3-O- and 6-O-Sulfation in Breast Cancer Cells: Prospects for Attenuating Prothrombotic Tumor Cell Activities

Article

作者: Bendas, Gerd ; Maccarana, Marco ; Li, Jin-ping ; König, Philipp ; Schulz-Fincke, Marie ; Bückreiß, Nico ; Götte, Martin ; van Kuppevelt, Toin H.

The deregulation of cell surface heparan sulfate proteoglycans (HSPGs) is a main issue of cancer cells for increasing their malignancy. In these terms, the sulfation pattern of HS, created by an orchestrated activity of enzymes balancing a site-specific sulfation, is of key importance. These enzymes are often deregulated by epigenetic processes in cancer, e.g., being silenced by DNA hypermethylation. Here, we address this issue in human breast cancer cell lines aiming to target epigenetic processes to reactivate HS sulfation, shifting HS into an antithrombotic phenotype for which 3-O-sulfation is particularly important. Treatment of MCF-7 and MDA-MB-231 cells with nontoxic concentrations of 5-azacytidine (azacytidine) and 5-fluoro-2'-deoxycytidine (FdCyd) as DNMT inhibitors or vorinostat for targeting HDAC increased HS3-O-sulfation remarkably, as confirmed by fluorescence microscopy, by upregulating HS3-O-sulfotransferases, detected by quantitative real-time polymerase chain reaction and Western blot. Flow cytometry and microscopic approaches confirm that upon inhibitor treatment, increased HS3-O-sulfation improves cell binding to antithrombin, leading to an antithrombotic activity. Nevertheless, only azacytidine- and vorinostat-treated cells display anticoagulative properties, represented by attenuated thrombin formation, a lower activation of human platelet aggregation, or ATP release. In contrast, FdCyd additionally upregulated tissue factor expression in both cell lines, overshadowing the anticoagulant effects of HS, leading to an overall prothrombotic phenotype. Our data provide evidence for the first time that targeting epigenetic processes in HS sulfation is a valuable means to foster anticoagulative cell properties for decreasing malignancy and metastatic potency. These data warrant further investigations to fine-tune epigenetic targeting and to search for potential biomarkers attributed to these activities.

2021-07-01·Cellular and Molecular Neurobiology3区 · 医学

Treatment with 5-fluoro-2-oxindole Increases the Antinociceptive Effects of Morphine and Inhibits Neuropathic Pain

3区 · 医学

Article

作者: Ferreira-Chamorro, Pablo ; Riego, Gabriela ; Pol, Olga ; Redondo, Alejandro

The efficacy of µ-opioid receptors (MOR) in neuropathic pain is low and with numerous side effects that limited their use. Chronic neuropathic pain is also linked with emotional disorders that aggravate the sensation of pain and which treatment has not been resolved. This study investigates whether the administration of an oxindole, 5-fluoro-2-oxindole, could inhibit the nociceptive and emotional behaviors and increase the effectiveness of morphine via modulating the microglia and activating the nuclear factor erythroid-2 related factor 2 (Nrf2) signaling pathway and MOR expression. In C57BL/6 mice with neuropathic pain provoked by the total constriction of sciatic nerve we studied the effects of 10 mg/kg 5-fluoro-2-oxindole in: (i) the allodynia and hyperalgesia caused by the injury; (ii) the anxiety- and depressive-like behaviors; (iii) the local antinociceptive actions of morphine; (iv) the expression of CD11b/c (a microglial marker), the antioxidant and detoxificant enzymes Nrf2, heme oxygenase 1 (HO-1) and NAD(P)H:quinone oxidoreductase-1 (NQO1), and of MOR in the spinal cord and hippocampus. Results showed that the inhibition of the main nociceptive symptoms and the anxiety- and depressive-like behaviors induced by 5-fluoro-2-oxindole were accompanied with the suppression of microglial activation and the activation of Nrf2/HO-1/NQO1 signaling pathway in the spinal cord and/or hippocampus. This treatment also potentiated the pain-relieving activities of morphine by normalizing the reduced MOR expression. This work demonstrates the antinociceptive, anxiolytic and antidepressant effects of 5-fluoro-2-oxindole, suggests a new strategy to enhance the antinociceptive actions of morphine and proposes a new mechanism of action of oxindoles during chronic neuropathic pain.

2020-11-01·Heliyon

Experimental approach, theoretical investigation and molecular docking of 2- chloro-5-fluoro phenol antibacterial compound

Article

作者: Arivazhagan, M ; Austine, A ; Vidhya, V

The molecular structural dimerization of biologically potent 2-chloro-5-fluoro phenol (2C5FP) is optimized. A combined experimental and theoretical characteristics of vibrational spectral determinations (NMR, FT-IR and Raman) on 2-chloro-5-fluoro phenol (2C5FP) were used at DFT-B3LYP/6-31++G (d,p) level of computation. A close coherence is achieved when experimentally observed wave numbers are compared with calculated wave numbers by refinement of the scale factors. Calculated values of global chemical descriptors of the present molecule reveal significant molecular stability and chemical reactivity. Non-Linear optical (NLO) property of the present molecule is investigated by determining the second order non linear parameter of first hyperpolarizability β. Moreover, hydrogen bond and thermodynamic parameters at various temperatures are determined and discussed. Investigated compound 2C5FP possesses a better antibacterial activity against Echerichia coli, Streptococcus aureus, Pseudomonas aureus,and Staphylococcus aureus, respectively. The title molecule is subjected to molecular docking studies with two different proteins, namely Staphylococcus aureus Tyrosyl-tRNA synthetase (PDB ID: 1JIL) and human dihydroorotate dehydrogenase (hDHODH) (PDB ID: 6CJF). The results of molecular docking analysis support the antibacterial activity and demonstrate a strong interaction with the DHODH inhibitor.

100 项与 FdCyd 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12957

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
成人急性髓性白血病	临床2期	美国	City of Hope National Medical Center	2009-12-01
复发性急性髓细胞白血病	临床2期	美国	City of Hope National Medical Center	2009-12-01
继发性骨髓增生异常综合征	临床2期	美国	City of Hope National Medical Center	2009-12-01
晚期非小细胞肺癌	临床2期	美国	National Cancer Institute	2009-08-20
膀胱癌	临床2期	美国	National Cancer Institute	2009-08-20
乳腺癌	临床2期	美国	National Cancer Institute	2009-08-20
头颈部肿瘤	临床2期	美国	National Cancer Institute	2009-08-20
晚期癌症	临床2期	美国	National Cancer Institute	1999-04-01
晚期恶性实体瘤	临床前	美国	National Cancer Institute	2012-03-05

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01479348 (CTgov)	早期临床1期	肺癌 \| 乳腺癌 \| 膀胱癌 \| 头颈部肿瘤	5	Positron emission tomography (PET)/Computed tomography (CT)+Tetrahydrouridine intravenous (IV)+[F-18]-5-FLUORO-2'-DEOXYCYTIDINE	膚網獵壓餘鹽簾築襯觸(鏇艱艱構窪蓋蓋壓製遞) = 繭繭願構鏇齋齋鹹齋顧築壓築壓夢選顧夢願鏇 (遞積遞襯鹽築醖壓網廠, 積鏇網獵鹹憲鏇鑰艱範 ~ 遞醖壓製壓顧範鏇鹽蓋) 更多	-	2020-05-22
NCT00978250 (CTgov)	临床2期	肺癌 \| 乳腺癌 \| 膀胱癌 \| 非小细胞肺癌 \| 晚期非小细胞肺癌 \| 头颈部肿瘤	95	Tetrahydrouridine (THU)+5-Fluoro-2'-Deoxycytidine (FdCyd)	憲醖鹽範鏇繭選鏇膚鏇(顧齋窪淵膚廠蓋鬱齋選) = 選獵築獵顧遞窪餘顧壓願憲艱醖範壓鹹觸鹹夢 (壓糧選鏇鏇淵壓淵淵鏇, 壓觸廠廠糧壓鬱齋窪鑰 ~ 齋夢顧積選顧築糧糧艱) 更多	-	2019-12-27
NCT00359606 (Pubmed \| Cancer Chemother Pharmacol) 人工标引	临床1期	实体瘤	-	tetrahydrouridine+FdCyd	(衊鏇餘憲鹽鬱製淵網構) = 100 mg/m2/day FdCyd with 350 mg/m2/day THU 齋範艱蓋鬱襯襯餘艱壓 (衊窪鹹膚餘範顧淵簾衊 ) 更多	积极	2015-03-01
AACR2011	临床1期	-	51	5-fluoro-2′-deoxycytidine	鏇糧選鏇願蓋蓋積網壓(顧窪願鹽遞獵鬱憲餘鹽) = 淵糧簾艱膚遞遞積淵製願糧廠範壓構蓋構齋製 (襯餘艱窪製壓壓蓋餘壓 )	-	2011-04-15