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Last update 08 May 2025

DTYMK

Last update 08 May 2025

Basic Info

Synonyms

CDC8, deoxythymidylate kinase, dTMP kinase

+ [4]

Introduction

Catalyzes the phosphorylation of thymidine monophosphate (dTMP) to thymidine diphosphate (dTDP), the immediate precursor for the DNA building block dTTP, with ATP as the preferred phosphoryl donor in the presence of Mg(2+).

Drugs associated with DTYMK

TMPK inhibitors(Ghent University)

Target

DTYMK

Mechanism

DTYMK inhibitors

Active Org.-

Originator Org.

Ghent University

Active Indication-

Inactive Indication

Mycobacterium Tuberculosis, Susceptibility to Infection By

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

TK-666

Target

DTYMK

Mechanism

DTYMK inhibitors

Active Org.-

Originator Org.

AstraZeneca PLC

Active Indication-

Inactive Indication

Gram-Positive Bacterial Infections

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with DTYMK

100 Translational Medicine associated with DTYMK

0 Patents (Medical) associated with DTYMK

516

Literatures (Medical) associated with DTYMK

13 Mar 2025·Journal of Medicinal Chemistry

Thymidylate Kinase-Targeted Antimicrobial Peptides via Phage Display: A Novel Strategy against Gram-Negative Bacteria

Article

Author: Cha, Sina ; Xue, Chenyu ; Li, Yuwen ; Fang, Yuxin ; Zhao, Lu ; Dong, Na ; Hu, Mingyang

The rise of antimicrobial resistance (AMR) in Gram-negative bacteria, including Escherichia coli (E. coli), poses a major public health threat. This study aimed to address the limitations of existing antimicrobial peptides (AMPs) by designing hybrid peptides with enhanced targeting and antibacterial potency. Eight heptapeptide sequences were identified through phage display screening and hybridized with WP (WKKIWKPGIKKWIK), a peptide exhibiting weak antimicrobial activity against Gram-negative bacteria. The hybrid peptides were systematically evaluated for their antimicrobial activity, specificity, and biocompatibility. The hybrid peptide SWP exhibited superior antibacterial activity, particularly against E. coli K88 (TI = 2.378), and demonstrated specific binding to thymidylate kinase (TMK), a key bacterial enzyme. In vivo studies employing a mouse peritonitis model confirmed SWP's ability to reduce bacterial loads and mitigate tissue damage while maintaining excellent biocompatibility. These findings underscore SWP as a promising candidate for the development of targeted antimicrobial agents with enhanced specificity and stability for Gram-negative pathogens.

07 Feb 2025·Current Medicinal Chemistry

Exploring the Dynamics of Asparagus racemosus Phytochemicals as Dual Target Inhibitors of Monkeypox Virus

Article

Author: Mishra, Saurav Kumar ; Bourhia, Mohammed ; Chandra, Anshuman ; Akash, Shopnil ; Mitra, Namrata ; Jardan, Yousef A. Bin ; Georrge, John J. ; Singh, Nagendra ; Krishna, Nikita

Aim:This study aimed to screen the potential phytochemicals derived from Asparagus racemosus (Shatavari) against Thymidylate Kinase (TMPK) and D9 decapping enzyme, which is the vital target of the monkeypox virus and helps in the host-- pathogen interaction mechanism, using integrated docking, QSAR analysis, and a molecular dynamics approach.Background:The Monkeypox Virus (MPXV) is a recently emerging outbreak with ongoing infection cases. Drugs and vaccines for smallpox are being used to contain it. However, no specific drugs or vaccines are available to combat this infection.Methods:The TMPK and D9 decapping enzymes were retrieved from the MPXV virus UK strain in FASTA format. Due to the unavailability of an experimentally determined structure, the 3D structure was modelled via SWISS-MODEL and further enhanced and validated. The structure was subjected to docking analysis with the derived phytochemicals from Asparagus racemosus using a maestro module. The potential inhibitors were examined via QSAR analysis. Additionally, through MD simulation 250ns, the stability was analyzed, and the MM-GBSA was employed to calculate the binding affinities.Results:The molecular investigation revealed asparoside-C (PubChem ID: 158598) and asparoside-D (PubChem ID: 158597) to be potential hits among others for both targets (TMPK and D9 decapping enzyme) compared to the reference drugs, i.e., tecovirimat, brincidofovir, and cidofovir, possessing antiviral and required bioactivity analyzed via the ADME and QSAR analyses. Moreover, the simulation study of over 250ns revealed strong stability, followed by RMSD, RMSF, etc. The free energy calculation via MMGBSA exhibited strong affinities of asparoside-C and asparoside-D towards the TMPK and the D9 decapping enzyme according to their respective scores.result:The molecular investigation revealed Asparoside-C; (PubChem ID: 158598) and Asparoside-D (PubChem ID: 158597) as potential hits among others for both targets (TMPK and D9 decapping enzyme) compared to the reference drugs, i.e., Tecovirimat, Brincidofovir, and Cidofovir and also possess antiviral and required bioactivity analysed via the ADME and QSAR analysis. Moreover, the simulation study of over 250ns revealed strong stability, followed by their RMSD, RMSF, etc. The free energy calculation via MM-GBSA exhibited strong affinities of Asparoside-C and Asparoside-D towards the TMPK and the D9 decapping enzyme by their respective scores.Conclusion:The docking, QSAR, and simulation investigation revealed dual-target inhibitors activity of phytochemicals from Asparagus racemosus towards the MPXV via targeting TMPK and D9 decapping enzyme. It has been observed that asparoside-D and asparoside-C can potentially combat MPXV.

01 Feb 2025·Microbial Pathogenesis

Structural characterization, cytotoxicity, antibiofilm activity, and synergistic potential with molecular docking analysis of ibuprofen-derived hydrazide against bacterial pathogens

Article

Author: Carvalho Aguiar, Francisco Kauê ; Marinho, Emmanuel Silva ; Frota Araújo, Ingrid Maria ; Santos, Hélcio Silva Dos ; Costa, Renata Albuquerque ; Carneiro, Victor Alves ; Ferreira da Silva, Benise ; Mesquita Cajazeiras, Francisco Ferdinando ; Onassis Cardoso Viana Gomes, Akenaton ; Rodrigues Teixeira, Alexandre Magno ; Gomes Pereira, Antonio Mateus ; Marinho, Márcia Machado

The study investigates the synthesis, characterization, and antibacterial activity of an ibuprofen-derived hydrazide (HIDZ). It was synthesized and characterized using NMR spectroscopy, DFT Calculations, and ADMET studies. Furthermore, HIDZ cytotoxicity on L929 cells was evaluated using the MTT reduction assay. Antibacterial activity was assessed against Gram-positive and Gram-negative strains through the microdilution method. The combinatory potential of HIDZ was performed using the checkerboard test with β-lactam antibiotics, oxacillin (OXA), meropenem (MER), and cefepime (CPM). Antibiofilm activity was evaluated for biofilm inhibition and disruption, particularly in combination with OXA. Molecular docking analysis examined HIDZ interactions with Thymidylate kinase, DNA Gyrase B, and DNA Topoisomerase IV subunit B. The global chemical reactivity descriptors analysis revealed significant variations in the atomic centers' susceptibility, highlighting the environment's importance in determining the reactive behavior of HIDZ. Pharmacokinetic predictions indicated efficient permeability across biological membranes, suggesting favorable bioavailability. MTT experiment showed that HIDZ caused cytotoxicity on higher concentrations over L929 fibroblasts. HIDZ exhibited superior activity against Gram-positive strains compared to ibuprofen, with lower MIC and MBC values. Both compounds were ineffective against Gram-negative strains. However, HIDZ was able to inhibit the biofilm formation of the most tested strains. The combinatory effect shows an additive effect between HIDZ and β-lactams. However, the HIDZ/OXA combination improved biofilm disruption, achieving up to a 92 % reduction in residual biofilm and cell viability compared to the control. Molecular docking simulations showed that HIDZ may interact with bacterial enzymes, improving antibiotic efficiency. The study suggests that HIDZ has promising potential as an antibacterial and antibiofilm agent, particularly against Gram-positive bacteria and in combination with β-lactam antibiotics.

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DTYMK

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