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

作用方式

抑制剂

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

权益机构-

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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187

项与 FdCyd 相关的文献（医药）

2025-02-01·JCO Clinical Cancer Informatics

Methodologic Approach to Defining Comorbidities in a Cohort of Patients With Cancer: An Example in the Optimal Breast Cancer Chemotherapy Dosing Study

Article

作者: Bandera, Elisa V. ; Heon, Narre ; Burganowski, Rachael ; Griggs, Jennifer J. ; Liu, Raymond ; Ergas, Isaac J. ; Blinder, Victoria ; Kotsurovskyy, Yuriy ; Gallagher, Grace B. ; Nakata, Kanichi G. ; Aiello Bowles, Erin J. ; Laurent, Cecile A. ; Wang, Peng ; Kroenke, Candyce H. ; Persaud, Sonia ; Roh, Janise M. ; Tabatabai, Sara ; Kantor, Elizabeth D. ; Kolevska, Tatjana ; O'Connell, Kelli ; Valice, Emily ; Bhimani, Jenna ; Rivera, Donna R. ; Kushi, Lawrence H.

PURPOSEWe evaluated the definitions of five comorbidities (renal and hepatic impairments, anemia, neutropenia, and thrombocytopenia) in women with breast cancer using data from electronic health records.METHODS In 11,097 women receiving adjuvant chemotherapy for stage I-IIIA breast cancer at Kaiser Permanente Northern California or Kaiser Permanente Washington, we assessed comorbidity definitions in two commonly used lookback windows (1 year before diagnosis, T1; and extending until chemotherapy initiation, T1-2). Within each, we assessed data availability and agreement between International Classification of Diseases (ICD)–defined and lab-defined comorbidities of varying severity. To assess how different pieces of information may affect providers in making treatment decisions, we used multivariable logistic regression to evaluate four-category (with comorbidity indicated by both ICD and lab, ICD-only, lab-only, or neither) and collapsed binary (comorbidity indicated by either ICD or lab v neither) definitions in relation to first cycle chemotherapy dose reduction (FCDR). RESULTS Extending the lookback period to chemotherapy initiation increased laboratory data availability (missingness ≤4.1% in T1-2 v >40% in T1). Assessment of agreement guided selection of laboratory cutpoints. In both time periods, the four-category and binary comorbidity variables were associated with use of FCDR, but binary variables had larger cell sizes and more stability of regression models. Ultimately, the comorbidity variables in T1 were defined by a combination of either ICD/qualifying laboratory values. Results were similar in T1-2, except laboratory data alone outperformed the combination variable for renal and hepatic comorbidity. CONCLUSIONLeveraging both ICD and lab data and extending the lookback period to include postdiagnosis but prechemotherapy initiation may provide better capture of comorbidity. Future studies may consider validating our findings with a gold-standard comorbidity status and in other community health care settings.

2024-12-01·International Journal of Mass Spectrometry

Influence of 5-fluorination on the structure and glycosidic bond stability of the protonated canonical DNA and RNA cytidine nucleosides: Oh, what a difference the 2′-hydroxy substituent makes?

作者: Rodgers, M. T. ; Soley, E.O. ; Oomens, J. ; Soley, E. O. ; Berden, G. ; Devereaux, Zachary J. ; Rodgers, M.T.

Fluorinated nucleosides are well-established as anticancer and antiviral medications.As with many pharmaceuticals, the effects of fluorine modifications are often only partially understood.In this work, the effects of 5-fluorination of the cytosine nucleobase on the structures and glycosidic bond stabilities of the protonated canonical DNA and RNA cytidine nucleosides (dCyd and Cyd) are examinedIR multiple photon dissociation action spectroscopy experiments and electronic structure calculations are employed to probe the structural influences of 5-fluorination.Spectral signatures in the IR fingerprint and hydrogen-stretching regions indicate that 5-fluorination heavily directs for and solely produces O2 protonation para to the 5-fluoro substituent.This differs from the canonical cytidine nucleosides where roughly equal populations of O2 and N3 protonated structures were observedEnergy-resolved collision-induced dissociation experiments combined with survival yield analyses are performed to probe the influence of 5-fluorination on glycosidic bond stability.Trends in the energy-dependence of the survival yield curves indicate that 5-fluorination weakens the glycosidic bond, and that the influence of 5-fluorination on glycosidic bond stability is much greater for dCyd than Cyd.Theory also finds that 5-fluorination weakens the glycosidic bond but predicts that the influence of 5-fluorination on N-glycosidic bond stability is roughly the same for dCyd and Cyd.Oh, what a difference the 2′-hydroxy substituent makes

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.

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
晚期恶性实体瘤	临床2期	美国	National Cancer Institute	2012-03-05
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
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
晚期非小细胞肺癌	临床前	美国	National Cancer Institute	2009-08-20
膀胱癌	临床前	美国	National Cancer Institute	2009-08-20
乳腺癌	临床前	美国	National Cancer Institute	2009-08-20

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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	繭襯鹹製齋積鏇簾觸淵(憲鏇鏇鹽憲網糧範夢製) = 製鑰廠願淵憲選窪鹽淵鬱構構憲夢鑰顧壓築糧 (築憲選醖淵範蓋艱餘壓, 鬱製積繭艱範窪淵願築 ~ 願憲鑰鏇膚廠糧襯夢膚) 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)	憲鑰繭廠鏇廠構簾選繭(遞艱鹹糧襯積選艱膚壓) = 遞製憲鑰壓齋襯夢糧餘鹹觸鏇糧衊製積糧蓋積 (遞齋願構獵鏇艱鹽鹽壓, 積淵網餘選積網範壓糧 ~ 鬱範製網鑰鑰選膚觸糧) 更多	-	2019-12-27
NCT00359606 (Pubmed \| Cancer Chemother Pharmacol) 人工标引	临床1期	实体瘤	-	tetrahydrouridine+FdCyd	(淵製壓遞鑰遞鹽積選製) = 100 mg/m2/day FdCyd with 350 mg/m2/day THU 獵齋鑰壓顧鬱夢繭構願 (壓壓蓋觸構鑰範醖願繭 ) 更多	积极	2015-03-01
AACR2011	临床1期	-	51	5-fluoro-2′-deoxycytidine	窪選衊餘願蓋簾衊顧繭(鹹齋蓋製築網獵鏇繭艱) = 餘襯選構夢製鑰觸鑰製蓋鏇鹽鹽鹽築遞願鑰製 (鬱廠鏇壓鹹簾衊繭鑰構 )	-	2011-04-15