Deoxyguanosine kinaseCytosolicInhibitorsPhosphorylationThymidine kinaseSeveral deoxyribonucleosides and their nucleosideTriphosphateMonophosphateProtein kinaseTyrosine kinaseNucleotidePhosphorylatesUridineDeoxythymidineMitochondrialPerturbationCytarabineGenePyrimidineExpressionMutationPhosphofructokinaseActivityPatientsCellsActivation
Deoxyguanosine kinase6
- 14 Ara-GMP is then monophosphorylated by deoxyguanosine kinase and deoxycytidine kinase to ara-G diphosphate, and then subsequently to the active ara-G triphosphate (ara-GTP). (drugbank.com)
- In mammalian cells, the phosphorylation of purine deoxyribonucleosides is mediated predominantly by two deoxyribonucleoside kinases, cytosolic deoxycytidine kinase and mitochondrial deoxyguanosine kinase. (nih.gov)
- Deoxyguanosine kinase deficiency: a report of four patients. (nih.gov)
- Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension. (nih.gov)
- Post mortem identification of deoxyguanosine kinase (DGUOK) gene mutations combined with impaired glucose homeostasis and iron overload features in four infants with severe progressive liver failure. (nih.gov)
- We applied real-time PCR method to assess the mRNA expression of equilibrative and concentrative nucleoside transporter (hENT1, hCNT1), deoxycytidine and deoxyguanosine kinase (dCK, dGK), 5'-nucleotidase (5'-NT), ribonucleotide reductase catalytic and regulatory (RR1, RR2) subunits in bone marrow cells from 32 patients with Waldenstr�m's Macroglobulinemia (WM) and small lymphocytic lymphoma (SLL) who received 2CdA-based chemotherapy. (vu.nl)
Cytosolic3
- 2. Intracellular cytarabine triphosphate production correlates to deoxycytidine kinase/cytosolic 5'-nucleotidase II expression ratio in primary acute myeloid leukemia cells. (nih.gov)
- Resistance to it in AML cells was shown to be linked to aberrant expression of equilibrative nucleoside transporters (ENT1) and metabolic enzymes deoxycytidine kinase (DCK) and cytosolic 5'-nucleotidase-II (NT5C2). (cancertools.org)
- Area durability, beat period, temperature, electroporation mass media, siRNA concentration, between other concerns were screened in order to receive roughly 70-80% mRNA and also molecule action downregulation with the cytosolic chemical deoxycytidine kinase (dCK), required for nucleoside analogue service. (proteasesignaling.com)
Inhibitors3
- Altogether, this study establishes ZOL-1 as a safe and effective treatment against GBM and provides a foundation to conduct further studies evaluating its potential as an effective adjuvant with other chemotherapies and kinase inhibitors. (bvsalud.org)
- Trethera's lead program combines TRE-515, a novel deoxycytidine kinase inhibitor, with de novo pathway inhibitors. (thevirusproject.org)
- Masitinib, as well as other protein kinase inhibitors, such as imatinib, interact with dCK and provoke an unforeseen conformational-dependent activation of this nucleoside kinase, modulating phosphorylation of nucleoside analogue drugs. (crcm-marseille.fr)
Phosphorylation7
- An enzyme that catalyzes reversibly the phosphorylation of deoxycytidine with the formation of a nucleoside diphosphate and deoxycytidine monophosphate. (nih.gov)
- Required for the phosphorylation of the deoxyribonucleosides deoxycytidine (dC), deoxyguanosine (dG) and deoxyadenosine (dA). (nih.gov)
- Deoxycytidine kinase (DCK) is required for the phosphorylation of several deoxyribonucleosides and their nucleoside analogs. (nih.gov)
- Phosphorylation of dUMP BY CMP-dCMP-UMP-dUMP kinase was inhibited competitively by DCMP and dTMP with Ki's of 6.9 X 10(-4) and 3.0 X 10(-3) M, respectively, and phosphorylation of dCMP was inhibited completely by dUMP a Ki of 2.2 X 10(-3) M. Relative Vmax activity of this enzyme was 345 nmoles/mg protein with dCMP and 127 nmoles/mg protein with dUMP. (mcw.edu)
- Today, it is well-known that almost all processes regulated by protein phosphorylation are reversible and controlled by the combined action of two different classes of enzymes, namely protein kinases and phosphatases. (biomedcentral.com)
- This phenomenon leads to an increase of prodrug phosphorylation of most of the chemotherapeutic drugs activated by this nucleoside kinase. (crcm-marseille.fr)
- Elevated intracellular uptake of 2deoxyadenosine accompanied by phosphorylation by deoxycytidine kinase results in deposition of deoxyadenosine triphosphate (dATP) which inhibits ribonucleotide reductase, stopping regular DNA fix and synthesis [5]. (siamtech.net)
Thymidine kinase2
- It targets the underlying pathophysiology of Thymidine kinase 2 deficiency (TK2d) by restoring mitochondrial DNA (mtDNA) replication fidelity. (ucb.com)
- Deoxynucleoside therapy for respiratory involvement in adult patients with thymidine kinase 2-deficient myopathy. (institut-myologie.org)
Several deoxyribonucleosides and their nucleoside1
- One hypothesis for the functionality of the "open" conformation is that the "open" conformation may assist in the initial nucleoside binding and the release of the monophosphate product Deoxycytidine kinase (dCK) phosphorylates several deoxyribonucleosides and their nucleoside analogues (a nucleoside with a sugar and a different nucleic acid base substitute or analogue that has unique properties when modified) using phosphate groups from ATP and UTP. (wikipedia.org)
Triphosphate3
- Conversely, increased deoxycytidine kinase activity is associated with increased activation of these agents to cytotoxic nucleoside triphosphate derivatives. (wikipedia.org)
- Combined inhibition of ribonucleotide reductase and deoxycytidine kinase (dCK) in multiple cancer cell lines depletes deoxycytidine triphosphate pools leading to DNA replication stress, cell cycle arrest and apoptosis. (trethera.com)
- All natural nucleoside triphosphates, except deoxycytidine triphosphate, can act as donors. (nih.gov)
Monophosphate2
- dCK predominantly phosphorylates deoxycytidine (dC) and converts dC into deoxycytidine monophosphate. (wikipedia.org)
- It was found that there are two kinds of pyrimidine nucleoside, monophosphokinase deoxythymidine 5'-monophosphate-deoxyuridine 5'-monophosphate (dTMP-dUMP) kinase and cytidine 5'-monophosphate-deoxycytidine 5'-monophosphate-uridine 5'-monophosphate-doexyuridine 5'-monophosphate (CMP-dCMP-UMP-dUMP) kinase, and their molecular weights were calculated to be 46,000 and 26,000, respectively, by gel filtration. (mcw.edu)
Protein kinase3
- Dual protein kinase and nucleoside kinase modulators for rationally designed polypharmacology. (crcm-marseille.fr)
- Masitinib, a highly selective protein kinase inhibitor, can sensitise gemcitabine-refractory cancer cell lines when used in combination with gemcitabine. (crcm-marseille.fr)
- The unforeseen dual activity of protein kinase inhibition/nucleoside kinase activation could be of great therapeutic benefit, through either reducing toxicity of therapeutic agents by maintaining effectiveness at lower doses or by counteracting drug resistance initiated via down modulation of dCK target. (crcm-marseille.fr)
Tyrosine kinase2
- Those responses were correlated with kinetic changes in the cell cycle or with changes in receptor tyrosine kinase signaling. (snmjournals.org)
- Cytarabine resistance was found by the inventors of these cell lines to lead to glucocorticoid sensitivity as long as the cells had a wild- type fms like tyrosine kinase 3 (FLT-3) gene. (cancertools.org)
Nucleotide1
- Previously, deoxycytidine kinase (dCK), a salvage pathway enzyme of nucleotide biosynthesis, was reported as an alternative molecular target for MTX by affinity purification using styrene glycinemethacrylate (SG) beads from cytoplasmic extracts of the human acute monocytic leukemia cell line THP-1 [3]. (cell-metabolism.com)
Phosphorylates1
- Deoxycytidine kinase phosphorylates cladribine to CdATP, which incorporates into DNA, leading to DNA strand breaks and inhibition of DNA synthesis. (nih.gov)
Uridine1
- In contrast to 2'-OH-containing pyrimidine ribonucleosides, which rely upon uridine-cytidine kinase 2 (UCK2) for activation, 2'-AzCyd is phosphorylated by deoxycytidine kinase (dCK), and we find that expression of dCK mediates cell-selective 2'-AzCyd labeling. (princeton.edu)
Deoxythymidine2
- MT1621 is an investigational therapy that combines two small molecules, deoxycytidine (dC) and deoxythymidine (dT). (ucb.com)
- For the first time, a Spanish team has studied the effects of this treatment based on nucleosides (deoxythymidine and deoxycytidine) orally on the respiratory function of 6 persons with TK2-deficient myopathy for an average of 30 months (8 to 48 months). (institut-myologie.org)
Mitochondrial1
- Thymidin kinase 2-deficient myopathy (TK2-deficient myopathy) is a rare mitochondrial disease of varying severity. (institut-myologie.org)
Perturbation1
- 600 genes differentially expressed following the PDK1_knockout_265_GSE42187 kinase perturbation from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset. (maayanlab.cloud)
Cytarabine2
- 5. Clofarabine exerts antileukemic activity against cytarabine-resistant B-cell precursor acute lymphoblastic leukemia with low deoxycytidine kinase expression. (nih.gov)
- It appears that the balance of kinase and deaminase levels may be an important factor in determining sensitivity or resistance of the cell to cytarabine. (nih.gov)
Gene1
- Deoxycytidine kinase (dCK) is an enzyme which is encoded by the DCK gene in humans. (wikipedia.org)
Pyrimidine2
- The major function of the pyrimidine nucleoside kinases is to maintain a cellular balance between the level of pyrimidine nucleosides and pyrimidine nucleoside monophosphates. (golifescience.com)
- However, since the overall cellular and plasma concentrations of the pyrimidine nucleosides, as well as those of ribose-1-phosphate, are low, the salvage of pyrimidines by these kinases is relatively inefficient. (golifescience.com)
Expression2
- 12. Melatonin overcomes resistance to clofarabine in two leukemic cell lines by increased expression of deoxycytidine kinase. (nih.gov)
- 14 Since T lymphoblasts have a higher expression of deoxycytidine kinase, ara-G preferentially accumulates in T cells over B cells, thus showing higher toxicity to T lymphoblasts. (drugbank.com)
Mutation1
- The pathogenesis of HCL was clarified by the discovery of its underlying genetic cause, the BRAF V600E kinase-activating mutation, which is somatically and clonally present in almost all patients through the entire disease spectrum and clinical course. (medscape.com)
Phosphofructokinase1
- Other members of this family (also known as the RK family) include ribokinase (RK), inosine-guanosine kinase, fructokinase, and 1-phosphofructokinase. (wikipedia.org)
Activity1
- Deoxycytidine prevents or delays (but does not reverse) the cytotoxic activity. (nih.gov)
Patients1
- Relationship between deoxycytidine kinase (DCK) genotypic variants and fludarabine toxicity in patients with follicular lymphoma. (cdc.gov)
Cells1
- Considered one of the basic challenges is only constrained in formation is obtainable about the creation of an artificial niche to keep implanted stem progenitor cells in an en vironment keeping competence for regeneration. (agckinase.com)
Activation1
- 16. Activation of deoxycytidine kinase by various nucleoside analogues. (nih.gov)