更新于：2024-11-01

Dm-dNK

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与 Dm-dNK 相关的药物

SG500-dNK

靶点

Dm-dNK

作用机制

Dm-dNK调节剂

在研机构-

原研机构

中国医科大学附属第一医院

在研适应症-

非在研适应症

乳腺癌

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

ZD55-Dm-dNK

靶点

Dm-dNK

作用机制

Dm-dNK调节剂

在研机构-

原研机构

中国医科大学附属第一医院

在研适应症-

非在研适应症

结直肠癌

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 Dm-dNK 相关的临床结果

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100 项与 Dm-dNK 相关的转化医学

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0 项与 Dm-dNK 相关的专利（医药）

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项与 Dm-dNK 相关的文献（医药）

2020-12-01·Nucleosides, Nucleotides & Nucleic Acids4区 · 生物学

The expression and activity of thymidine kinase 1 and deoxycytidine kinase are modulated by hydrogen peroxide and nucleoside analogs

4区 · 生物学

Article

作者: Sun, Ren ; Eriksson, Staffan ; Wang, Liya

Thymidine kinase 1 (TK1) and deoxycytidine kinase (dCK) are required for the activation of thymidine and deoxycytidine analogs used in antiviral and anticancer therapies. Many anticancer drugs cause oxidative stress, and the rise of GSSG and other reactive oxygen species may lead to alteration in gene expression, protein, nucleic acids and lipid modifications. Here, we investigated the effects of oxidative stress and nucleoside analog on the expression and activity of TK1 and dCK. Treatment with GSSG resulted in glutathionylation of dCK and dGK but not TK1 and Dm-dNK, and glutathionylation led to increased dCK activity but decreased dGK activity. Treatment with hydrogen peroxide resulted in induction of TK1, however, the TK1 activity did not correlate with TK1 protein levels, indicating that TK1 protein was inactive. The cellular expression of dCK, however, was reduced but dCK activity was not affected at concentration ≤ 4 mM. Treatment with TFT or 5FdU resulted in downregulation of both TK1 and dCK. However, araC and dFdC treatment led to increased dCK protein but decreased dCK activity. In contrast, both TK1 protein and activity were upregulated after araC and dFdC treatment. Doxorubicin treatment led to upregulation of the TK1 but downregulation of dCK. In conclusion TK1 and dCK expression and activity are apparently affected by oxidative stress and treatment by nucleoside analogs. These results demonstrate the pharmacokinetic importance of characterizing the expression and activity of TK1 and dCK during chemotherapy with thymidine and deoxycytidine analogs in order to optimize their efficacy.

2016-12-01·Nucleosides, Nucleotides & Nucleic Acids4区 · 生物学

Isolation of a novel protein, P12—from adultDrosophila melanogasterthat inhibits deoxyribonucleoside and protein kinase activities and activates 3′-5′- exonuclease activity

4区 · 生物学

Article

作者: van Zanten, Gabriella ; Berenstein, Dvora ; Munch-Petersen, Birgitte ; Kjærulff, Søren ; Søndergaard, Leif ; Christiansen, Louise Slot ; Lauridsen, Marianne

We have previously found that Drosophila melanogaster only has one deoxyribonucleoside kinase, Dm-dNK, however, capable to phosphorylate all four natural deoxyribonucleosides. Dm-dNK was originally isolated from an embryonic cell line. We wanted to study the expression of Dm-dNK during development from embryonic cells to adult flies and found declining Dm-dNK activity during development and no activity in adult flies. Surprisingly, the extract from adult flies exhibited a strong inhibitory effect on deoxyribonucloside kinase activity. The dNK-inhibitor was precipitable with ammonium sulfate, and was purified to a high degree by gel-filtration as indicated by LC-MS/MS analysis. Since the inhibitor eluted from G-200 gel-filtration with a size of 10-13 kDa, we named it P12. We tested the purified fraction for specificity towards various enzymes and found that both mammalian and bacterial dNKs were inhibited, whereas there was no effect on hexokinase and pyruvate kinases and acidic phosphatase. However, when tested against cyclin B-dependent kinase, we found a strong inhibitory effect. Both with human Cdk1/CycB and S. pombe Cdc2/B-type cyclin the purified fraction from Superdex 200 that inhibited Dm-dNK, also inhibited the two protein kinases to the same degree. Furthermore, testing P12 in a DNA polymerase based assay we found that the 3'-5'-exonuclease part of the DNA polymerase (Klenow polymerase) was activated.

2014-11-01·Journal of Biological Chemistry2区 · 生物学

Long Term Expression of Drosophila melanogaster Nucleoside Kinase in Thymidine Kinase 2-deficient Mice with No Lethal Effects Caused by Nucleotide Pool Imbalances

2区 · 生物学

Article

作者: Zhou, Xiaoshan ; Krishnan, Shuba ; Curbo, Sophie ; Paredes, João A ; Kuiper, Raoul V ; Hultenby, Kjell ; Karlsson, Anna

Mitochondrial DNA depletion caused by thymidine kinase 2 (TK2) deficiency can be compensated by a nucleoside kinase from Drosophila melanogaster (Dm-dNK) in mice. We show that transgene expression of Dm-dNK in Tk2 knock-out (Tk2(-/-)) mice extended the life span of Tk2(-/-) mice from 3 weeks to at least 20 months. The Dm-dNK(+/-)Tk2(-/-) mice maintained normal mitochondrial DNA levels throughout the observation time. A significant difference in total body weight due to the reduction of subcutaneous and visceral fat in the Dm-dNK(+/-)Tk2(-/-) mice was the only visible difference compared with control mice. This indicates an effect on fat metabolism mediated through residual Tk2 deficiency because Dm-dNK expression was low in both liver and fat tissues. Dm-dNK expression led to increased dNTP pools and an increase in the catabolism of purine and pyrimidine nucleotides but these alterations did not apparently affect the mice during the 20 months of observation. In conclusion, Dm-dNK expression in the cell nucleus expanded the total dNTP pools to levels required for efficient mitochondrial DNA synthesis, thereby compensated the Tk2 deficiency, during a normal life span of the mice. The Dm-dNK(+/-) mouse serves as a model for nucleoside gene or enzyme substitutions, nucleotide imbalances, and dNTP alterations in different tissues.