FdCyd(FdCyd) - 药物靶点：DNMT1_在研适应症：晚期恶性实体瘤_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)、表观遗传学药物

治疗领域

肿瘤

在研适应症

晚期恶性实体瘤

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+ [5]

原研机构

City of Hope National Medical Center

在研机构

National Cancer Institute

非在研机构

City of Hope National Medical Center

权益机构-

最高研发阶段临床1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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154

项与 FdCyd 相关的文献（医药）

2025-06-24·ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

In Quest of Chemical Probes for DNA Methylation Reader Proteins: Nucleoside and Dimer Analogues of 5‐Methylcytosine Interact with MBD2

Article

作者: Dr. Gianluca Sbardella ; Dr. Paola B. Arimondo ; Dr. J. Iñaki Guijarro ; Dr. Jean Contreras ; Dr. Sophie Vichier-Guerre ; Dr. Minh-Ha Nguyen ; Corinne Jallet ; Dr. Alessandra Feoli ; Dr. Bruno Vitorge ; Frédéric Bonhomme ; Laurence Dugué

Abstract:

DNA methylation modulates gene expression without altering the DNA sequence. Aberrant DNA methylation patterns characterise a wide range of diseases, from cancer to neurological disorders, and serve as validated therapeutic targets and diagnostic tools. Among the proteins involved in DNA methylation regulation, the human reader methyl‐CpG binding domain 2 protein (MBD2) exhibits a strong preference for methylated DNA and initiates signalling cascades predominantly resulting in gene repression. The full description of this mechanism is still to be elucidated. Here, we developed original chemical compounds to interfere with MBD2 and its interaction with DNA. Through convergent chemical pathways, we modified 5‐methylcytosine at position N4 and synthesised the corresponding deoxynucleosides and CpG dimers. We tested 70 compounds in two screening assays to assess their interaction with MBD2 and their ability to disrupt the MBD2/DNA complex. Remarkably, substituting modified nucleobases into CpG dimers significantly boosted the biological activity. Furthermore, we investigated the impact of the configuration ( d/l ) of the modified nucleosides and identified four dimers ( 5d , 7e , 15e and 16e ) able to disrupt the MBD2/DNA complex, highlighting the advantage of the l ‐configuration. Importantly, NMR experiments confirmed their interaction with amino acids of MBD2 involved in methylated DNA binding.

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

PURPOSE:

We 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.

CONCLUSION:

Leveraging 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.

2025-01-01·Current Research in Food Science

Deoxynucleosides as promising antimicrobial agents against foodborne pathogens and their applications in food and contact material surfaces

Article

作者: Lee, Jintae ; Lee, Jin-Hyung ; Faleye, Olajide Sunday

V. parahaemolyticus biofilms accumulate on various seafoods and contact surfaces where they induce cross-contamination, spoilage and persistence in the food industry. Recently, nucleosides are being repurposed for antibacterial and technological applications including preservation and flavor enhancement. Therefore, for the first time, we explored the effects of various nucleosides against the biofilm and planktonic lifestyles of Vibrio spp, vis-à-vis the mechanisms, synergism with food additive, food and surface decontamination potentials. Among the sixty-six nucleosides evaluated, 2',3'-dideoxyadenosine (ddA) and 2'-deoxy-5-fluorocytidine (FdCyd) were identified as exceptional biofilm inhibitors, achieving 98 and 100 % reduction respectively. FdCyd exhibited low minimum inhibitory concentration (MIC) of 30, 40 and 10 μg/mL against V. parahaemolyticus, V. harveyi and Salmonella typhimurium while ddA had MICs 40, 40 and >500 μg/mL, respectively. Also, the nucleosides disrupted Vibrio biofilm architecture and caused loss of cell membrane integrity mediated by oxidative stress. Their combinations with sodium tripolyphosphate, a known food additive enhanced antimicrobial activities against V. parahaemolyticus by 4-16-folds. While FdCyd significantly inhibited mixed-biofilm formation of Vibrio and Salmonella, both nucleosides eradicated pre-formed biofilms from food contact surfaces, and showed preservative potentials in squid. Notably, they downregulated genes encoding biofilms and quorum sensing (aphA, cpsA, luxS & opaR), outer membrane (tolC), response regulators (toxR, rpoS) and DNA synthesis (dnaE) as revealed by transcriptomic studies. These results demonstrate that nucleosides, especially FdCyd are promising novel compounds for controlling biofilm formation, maintaining hygiene and safety in food industry.

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
肺癌	临床2期	美国	National Cancer Institute	2009-08-20
晚期恶性实体瘤	临床1期	美国	National Cancer Institute	2012-03-05
成人急性髓性白血病	临床1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1期	美国	City of Hope National Medical Center	2009-12-01
晚期癌症	临床1期	美国	City of Hope National Medical Center	1999-04-01

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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 ... 更多	5	Positron emission tomography (PET)/Computed tomography (CT)+Tetrahydrouridine intravenous (IV)+[F-18]-5-FLUORO-2'-DEOXYCYTIDINE	範鏇餘築願壓憲夢鏇網 = 糧獵醖衊糧衊淵顧餘憲窪構淵壓鏇網醖築簾網 (憲鏇範鹹衊選齋壓壓衊, 艱築構獵簾構構襯顧範 ~ 選網獵淵鬱糧憲選積齋) 更多	-	2020-05-22
NCT00978250 (CTgov)	临床2期	肺癌 \| 乳腺癌 \| 非小细胞肺癌 ... 更多	95	Tetrahydrouridine (THU)+5-Fluoro-2'-Deoxycytidine (FdCyd)	願鏇構積鹽網膚衊簾簾 = 蓋衊夢鏇簾膚鏇艱衊鹽淵艱壓艱廠選鹽構廠觸 (鏇醖構窪餘獵鏇蓋壓鑰, 構構觸蓋壓積衊製蓋鹽 ~ 積積願鏇窪簾醖鏇夢餘) 更多	-	2019-12-27
NCT00359606 (Pubmed \| Cancer Chemother Pharmacol) 人工标引	临床1期	实体瘤	-	tetrahydrouridine+FdCyd	廠窪夢蓋鹹獵觸簾淵齋(築夢窪鏇獵齋構顧憲衊) = 100 mg/m2/day FdCyd with 350 mg/m2/day THU 獵製鬱醖繭窪壓憲壓鏇 (鑰襯鹽糧願糧憲餘糧齋 ) 更多	积极	2015-03-01
AACR2011	临床1期	-	51	5-fluoro-2′-deoxycytidine	範壓窪鏇鏇鏇窪壓壓簾(獵網繭簾鹽鹹簾鑰顧膚) = 憲遞壓廠遞蓋齋衊醖膚鹽醖齋獵顧顧顧窪淵網 (範襯簾淵鏇構齋範範襯 )	-	2011-04-15
ASCO2004	临床1期	晚期恶性实体瘤	14	Carboplatin	鹽獵簾獵蓋鏇餘簾願窪(廠襯窪鑰膚範艱獵糧鹽) = Other possible treatment-related toxicities included: nausea, vomiting, diarrhoea, fatigue, anorexia, anaemia (all ≤grade 2 and easily manageable) 艱鑰壓製遞鑰築鏇網夢 (糧齋構繭齋餘蓋艱衊餘 ) 更多	-	2004-07-15
Pubmed \| J Clin Oncol	临床2期	高危骨髓增生异常综合征	66	Low-dose 5-Aza-2'-deoxycytidine (DAC)	醖鬱膚鹽選膚蓋淵獵繭(壓鹹繭鏇壓願醖觸膚築) = 願網顧衊製餘觸構蓋齋顧鑰簾淵願廠餘繭膚鏇 (願願廠鏇製顧願齋餘簾 ) 更多	积极	2000-03-01