更新于：2024-09-19

DGUOK

更新于：2024-09-19

基本信息

别名

Deoxyadenosine kinase, mitochondrial、deoxyguanosine kinase、Deoxyguanosine kinase, mitochondrial

+ [2]

简介

Phosphorylates deoxyguanosine and deoxyadenosine in the mitochondrial matrix, with the highest efficiency for deoxyguanosine (PubMed:8692979, PubMed:8706825, PubMed:11687801, PubMed:17073823, PubMed:23043144). In non-replicating cells, where cytosolic dNTP synthesis is down-regulated, mtDNA synthesis depends solely on DGUOK and TK2. Phosphorylates certain nucleoside analogs (By similarity). Widely used as target of antiviral and chemotherapeutic agents.

关联

项与 DGUOK 相关的药物

[18F]F-AraG

靶点

DCK x DGUOK

作用机制

DCK inhibitors [+1]

在研机构

Stanford University [+1]

原研机构

Stanford University

在研适应症

非小细胞肺癌 [+7]

非在研适应症

新型冠状病毒感染 [+4]

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

CERC-913

靶点

DGUOK

作用机制

DGUOK agonists

在研机构

Cerecor, Inc. /Pediatric Assets/ [+2]

原研机构

Ichorion Therapeutics, Inc.

在研适应症

脱氧鸟苷激酶缺乏症 [+1]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

项与 DGUOK 相关的临床试验

NCT06414902 / Not yet recruiting早期临床1期IIT

18F-AraG PET/CT as a Non-Invasive Imaging Biomarker for Chemoradiation Treatment Response in Esophageal Cancer

To learn if 18F-FAraG PET scans can find tumors in participants with esophageal cancer and predict a participant's response to treatment.

开始日期2024-11-29

申办/合作机构

The University of Texas MD Anderson Cancer Center

NCT06457789 / Not yet recruitingN/A

Assessment of PET Tracers to Evaluate T Cell Change and Activation in Relation to Immunotherapy Treatment Response in Non-Small Cell Lung Cancer

The iRelate is a PET imaging trial to compare two upcoming and promising T cell PET tracers. Following chemo-immuno therapy, as part of standard care, NSCLC patients will be recruited to receive two PET scans, shortly before their surgery. Both PET scans will be compared to each other, as well as compared to the pathological analysis of the resected tumor.
This study will provide detailed information on the unique as well as additive capacities of imaging biomarkers derived from the immune cell targeting PET tracers.

开始日期2024-07-01

申办/合作机构

Stichting Onderzoek Cancer Center Amsterdam

[+1]

NCT06107374 / Not yet recruiting临床2期

Imaging of T-cell Activation With [18F]F-araG in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Undergoing PD-1/PD-L1 Directed Therapy

This pilot study uses [18F]F AraG PET imaging to evaluate the immunological response to checkpoint inhibitor therapy (CkIT) in patients with advanced NSCLC tumors. The study's main objectives are to quantify the change in [18F]F AraG PET signal before and while on CkIT therapy and to correlate this change in [18F]F AraG PET signal with radiographic response.
To explore these objectives, eligible subjects will undergo pre- and on - CkIT treatment [18F]F AraG PET/CT scans, and will be followed up for 12 months for assessment of radiographic and clinical outcomes. This study is a single-site, open label, non randomized, single arm pilot trial. Patients and care providers will not be blinded to any part of the study.

开始日期2023-11-01

申办/合作机构

CellSight Technologies, Inc.

100 项与 DGUOK 相关的临床结果

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100 项与 DGUOK 相关的转化医学

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0 项与 DGUOK 相关的专利（医药）

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220

项与 DGUOK 相关的文献（医药）

2024-05-03·Brain Communications

Deoxyguanosine kinase deficiency: natural history and liver transplant outcome

Article

作者: Cordelli, Duccio Maria ; Mayr, Johannes ; Cano, Aline ; Primiano, Guido ; Lamperti, Costanza ; Laborde, Nolwenn ; Schlieben, Lea Dewi ; Okazaki, Yasushi ; Procaccio, Vincent ; Lenz, Dominic ; Garone, Caterina ; Gaignard, Pauline ; La Morgia, Chiara ; Staufner, Christian ; Mancuso, Michelangelo ; Servidei, Serenella ; Taanman, Jan-Willem ; Tal, Galit ; Ronchi, Dario ; Nesbitt, Victoria ; Ticci, Chiara ; Montano, Vincenzo ; Murayama, Kei ; Shimura, Masaru ; Martinelli, Diego ; Petkovic Ramadza, Danijela ; Santer, René ; Manzoni, Eleonora ; Bris, Céline ; Procopio, Elena ; Karall, Daniela ; Musumeci, Olimpia ; Carli, Sara ; Hirano, Michio ; Carelli, Valerio ; Gonzales, Emmanuel ; Gasperini, Serena ; Barić, Ivo ; Menni, Francesca ; Rouzier, Cécile ; Prokisch, Holger ; Furlan, Francesca

AbstractAutosomal recessive pathogenetic variants in the DGUOK gene cause deficiency of deoxyguanosine kinase activity and mitochondrial deoxynucleotides pool imbalance, consequently, leading to quantitative and/or qualitative impairment of mitochondrial DNA synthesis. Typically, patients present early-onset liver failure with or without neurological involvement and a clinical course rapidly progressing to death.This is an international multicentre study aiming to provide a retrospective natural history of deoxyguanosine kinase deficient patients. A systematic literature review from January 2001 to June 2023 was conducted. Physicians of research centres or clinicians all around the world caring for previously reported patients were contacted to provide followup information or additional clinical, biochemical, histological/histochemical, and molecular genetics data for unreported cases with a confirmed molecular diagnosis of deoxyguanosine kinase deficiency.A cohort of 202 genetically confirmed patients, 36 unreported, and 166 from a systematic literature review, were analyzed. Patients had a neonatal onset (≤ 1 month) in 55.7% of cases, infantile (>1 month and ≤ 1 year) in 32.3%, pediatric (>1 year and ≤18 years) in 2.5% and adult (>18 years) in 9.5%. Kaplan-Meier analysis showed statistically different survival rates (P < 0.0001) among the four age groups with the highest mortality for neonatal onset. Based on the clinical phenotype, we defined four different clinical subtypes: hepatocerebral (58.8%), isolated hepatopathy (21.9%), hepatomyoencephalopathy (9.6%), and isolated myopathy (9.6%). Muscle involvement was predominant in adult-onset cases whereas liver dysfunction causes morbidity and mortality in early-onset patients with a median survival of less than 1 year. No genotype–phenotype correlation was identified. Liver transplant significantly modified the survival rate in 26 treated patients when compared with untreated. Only six patients had additional mild neurological signs after liver transplant.In conclusion, deoxyguanosine kinase deficiency is a disease spectrum with a prevalent liver and brain tissue specificity in neonatal and infantile-onset patients and muscle tissue specificity in adult-onset cases. Our study provides clinical, molecular genetics and biochemical data for early diagnosis, clinical trial planning and immediate intervention with liver transplant and/or nucleoside supplementation.

2024-04-01·Clinics and Research in Hepatology and Gastroenterology

A novel homozygous mutation, c.662_672del, in DGUOK gene causing mitochondrial DNA depletion syndrome of type hepatocerebral – A case report

Letter

作者: Ramesh, K V Raja ; Rajsekhar, Batchu ; Chitturi, Neelima ; Pemmasani, Sandhya Kiran ; Radhakrishna, Kandula ; Acharya, Anuradha

2024-02-01·Acta Biochimica et Biophysica Sinica

Mitochondrial deoxyguanosine kinase is required for female fertility in mice

Article

作者: Sang, Lei ; Yan, Jiacong ; Wu, Ze ; Chen, Huicheng ; Yang, Shengyu ; Yao, Xinyi ; Zuo, Xiaoyuan ; Sun, Jianwei ; Fan, Die ; Dong, Rui ; Wang, Xin ; Gao, Yake ; Zhang, Xu

Mitochondrial homeostasis plays a pivotal role in oocyte maturation and embryonic development. Deoxyguanosine kinase (DGUOK) is a nucleoside kinase that salvages purine nucleosides in mitochondria and is critical for mitochondrial DNA replication and homeostasis in non-proliferating cells. Dguok loss-of-function mutations and deletions lead to hepatocerebral mitochondrial DNA deletion syndrome. However, its potential role in reproduction remains largely unknown. In this study, we find that Dguok knockout results in female infertility. Mechanistically, DGUOK deficiency hinders ovarian development and oocyte maturation. Moreover, DGUOK deficiency in oocytes causes a significant reduction in mitochondrial DNA copy number and abnormal mitochondrial dynamics and impairs germinal vesicle breakdown. Only few DGUOK-deficient oocytes can extrude their first polar body during in vitro maturation, and these oocytes exhibit irregular chromosome arrangements and different spindle lengths. In addition, DGUOK deficiency elevates reactive oxygen species levels and accelerates oocyte apoptosis. Our findings reveal novel physiological roles for the mitochondrial nucleoside salvage pathway in oocyte maturation and implicate DGUOK as a potential marker for the diagnosis of female infertility.